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1. Species-Specific Molecular Barriers to SARS-CoV-2 Replication in Bat Cells

Author: Sophie-Marie Aicher, Felix Streicher, Maxime Chazal, Delphine Planas, Dongsheng Luo, Julian Buchrieser, Monika Nemcova, Veronika Seidlova, Jan Zukal, Jordi Serra-Cobo, Dominique Pontier, Bertrand Pain, Gert Zimmer, Olivier Schwartz, Philippe Roingeard, Jiri Pikula, Laurent Dacheux, Nolwenn Jouvenet, Signalisation antivirale - Virus sensing and signaling, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Virus et Immunité - Virus and immunity, Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology, Institut Pasteur [Paris]-Université Paris Cité (UPCité), University of Veterinary and Pharmaceutical Sciences [Brno] (VFU), Universitat de Barcelona (UB), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (U1208 Inserm - UCBL1 / SBRI - USC 1361 INRAE), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Bern, Institute of Virology and Immunology [Mittelhäusern] (IVI), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), This study was funded by the CNRS (N.J. and O.S.), Institut Pasteur (N.J., L.D., and O.S.), the 'Urgence COVID-19' fundraising campaign of Institut Pasteur (N.J., L.D., and O.S.), the University of Veterinary Sciences Brno (FVHE/Pikula/ITA2021) (J.P.), the FINOVI Fondation (AO13) and Covid IDEX Universite Lyon 1 (B.P.), LabEx Ecofect (ANR-11-LABX-0048) (Do.P.), Labex IBEID (ANR-10-LABX-62-IBEID) (O.S.), ANR/FRM Flash Covid PROTEO-SARS-CoV-2 (O.S.), and IDISCOVR (O.S.). S.-M.A. and De.P. are supported by the Pasteur-Paris University International Ph.D. Program and the Vaccine Research Institute (ANR-10-LABX-77), respectively. D.L. was funded by the Chinese Scholarship Council and Institut Pasteur. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI), Girard, Agnès, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, and Vaccine Research Institute [Créteil, France] (VRI)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 630 Agriculture, SARS-CoV-2, Immunology, coronavirus, Virus Replication, Microbiology, Species Specificity, Virology, Insect Science, Chiroptera, bat cells, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Animals, Humans, Receptors, Virus, Angiotensin-Converting Enzyme 2, innate immunity
Abstract: Bats are natural reservoirs of numerous coronaviruses, including the potential ancestor of SARS-CoV-2. Knowledge concerning the interaction between coronaviruses and bat cells is sparse. We investigated the ability of primary cells from Rhinolophus and Myotis species, as well as of established and novel cell lines from Myotis myotis, Eptesicus serotinus, Tadarida brasiliensis, and Nyctalus noctula, to support SARS-CoV-2 replication. None of these cells were permissive to infection, not even the ones expressing detectable levels of angiotensin-converting enzyme 2 (ACE2), which serves as the viral receptor in many mammalian species. The resistance to infection was overcome by expression of human ACE2 (hACE2) in three cell lines, suggesting that the restriction to viral replication was due to a low expression of bat ACE2 (bACE2) or the absence of bACE2 binding in these cells. Infectious virions were produced but not released from hACE2-transduced M. myotis brain cells. E. serotinus brain cells and M. myotis nasal epithelial cells expressing hACE2 efficiently controlled viral replication, which correlated with a potent interferon response. Our data highlight the existence of species-specific and cell-specific molecular barriers to viral replication in bat cells. These novel chiropteran cellular models are valuable tools to investigate the evolutionary relationships between bats and coronaviruses. IMPORTANCE Bats are host ancestors of several viruses that cause serious disease in humans, as illustrated by the ongoing SARS-CoV-2 pandemic. Progress in investigating bat-virus interactions has been hampered by a limited number of available bat cellular models. We have generated primary cells and cell lines from several bat species that are relevant for coronavirus research. The various permissivities of the cells to SARS-CoV-2 infection offered the opportunity to uncover some species-specific molecular restrictions to viral replication. All bat cells exhibited a potent entry-dependent restriction. Once this block was overcome by overexpression of human ACE2, which serves at the viral receptor, two bat cell lines controlled well viral replication, which correlated with the inability of the virus to counteract antiviral responses. Other cells potently inhibited viral release. Our novel bat cellular models contribute to a better understanding of the molecular interplays between bat cells and viruses.
Published: 2022

2. Structural basis of synergistic neutralization of Crimean-Congo hemorrhagic fever virus by human antibodies

Author: Akaash K. Mishra, Jan Hellert, Natalia Freitas, Pablo Guardado-Calvo, Ahmed Haouz, J. Maximilian Fels, Daniel P. Maurer, Dafna M. Abelson, Zachary A. Bornholdt, Laura M. Walker, Kartik Chandran, François-Loïc Cosset, Jason S. McLellan, Felix A. Rey, University of Texas at Austin [Austin], Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cristallographie (Plateforme) - Crystallography (Platform), Albert Einstein College of Medicine [New York], Adimab LLC, Mapp Biopharmaceutical Inc., This work was supported by National Institutes of Health award U19 AI142777 to J.S.M., Z.A.B., K.C., and L.M.W., as well as by Institut Pasteur, CNRS and grant ANR-10-LABX-62-10 IBEID to F.A.R. and by the LabEx Ecofect (ANR-11-LABX-0048) of the 'Université de Lyon,' within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR), to F.-L.C. Research was funded in part by Welch Foundation grant F-0003-19620604 awarded to J.S.M. The Pasteur-Cantarini 24-month fellowship was granted to J.H., who was further supported by the Région Ile de France (Domaine d’intérêt majeur - innovative technologies for life sciences, DIM 1HEALTH)., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ribierre, Hélène, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, and PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID
Subjects: Models, Molecular, Protein Folding, Multidisciplinary, Protein Conformation, [SDV]Life Sciences [q-bio], Virus Internalization, Antibodies, Viral, Crystallography, X-Ray, Antibodies, Neutralizing, Article, [SDV] Life Sciences [q-bio], Epitopes, Immunoglobulin Fab Fragments, Protein Domains, Neutralization Tests, Hemorrhagic Fever Virus, Crimean-Congo, Humans, Protein Multimerization, Viral Fusion Proteins, Protein Binding
Abstract: International audience; Crimean-Congo hemorrhagic fever virus (CCHFV) is the most widespread tick-borne zoonotic virus, with a 30% case fatality rate in humans. Structural information is lacking in regard to the CCHFV membrane fusion glycoprotein Gc-the main target of the host neutralizing antibody response-as well as antibody-mediated neutralization mechanisms. We describe the structure of prefusion Gc bound to the antigen-binding fragments (Fabs) of two neutralizing antibodies that display synergy when combined, as well as the structure of trimeric, postfusion Gc. The structures show the two Fabs acting in concert to block membrane fusion, with one targeting the fusion loops and the other blocking Gc trimer formation. The structures also revealed the neutralization mechanism of previously reported antibodies against CCHFV, providing the molecular underpinnings essential for developing CCHFVspecific medical countermeasures for epidemic preparedness.
Published: 2022

3. Puumala Virus Variants Circulating in Forests of Ardennes, France: Ten Years of Genetic Evolution

Author: Franck Boué, Jordi Serra-Cobo, Séverine Murri, Mathilde Couteaudier, Dominique Pontier, Philippe Marianneau, Noël Tordo, Viviane Hénaux, Guillaume Castel, Denis Augot, Frank Sauvage, Marc López-Roig, Elodie Monchatre-Leroy, Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Laboratoire de la rage et de la faune sauvage de Nancy (LRFSN), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Institut de Recerca de la Biodiversitat - Biodiversity Research Institute [Barcelona, Spain] (IRBio UB), Universitat de Barcelona (UB), Department de Biologia Evolutiva, Ecologia i Ciències Ambientals, University of Barcelona, Laboratoire de Lyon [ANSES], Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Seenovate, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), LabEx Ecofect, Eco-Evolutionary Dynamics of Infectious Diseases, Stratégies Antivirales, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Institut Pasteur de Guinée, Réseau International des Instituts Pasteur (RIIP), This research was internally funded by the participating teams and received additional funding from ANSES (Afsset grant EST-2007-75) as well as EU grants FP7-261504 EDENext and FP7-278976 ANTIGONE and the LABEX ECOFECT (ANR-11-LABX-0048) of Université de Lyon., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), European Project: 261504,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EDENEXT(2011), European Project: 278976,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,ANTIGONE(2011), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), ANSES (Afsset grant EST-2007-75), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Institut Pasteur [Paris], Marchal-Mauer, Sophie, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, Biology and control of vector-borne infections in Europe - EDENEXT - - EC:FP7:HEALTH2011-01-01 - 2015-06-30 - 261504 - VALID, and ANTIcipating the Global Onset of Novel Epidemics - ANTIGONE - - EC:FP7:HEALTH2011-11-01 - 2016-10-31 - 278976 - VALID
Subjects: Microbiology (medical), Orthohantavirus, Rodent, Population, Zoology, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Article, 03 medical and health sciences, biology.animal, [SDV.BID.SPT] Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Myodes glareolus, evolution, Nephropathia epidemica, medicine, population dynamics, Immunology and Allergy, Seroprevalence, education, Virus Orthohantavirus, Molecular Biology, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, education.field_of_study, Genetic diversity, General Immunology and Microbiology, biology, seroprevalence, 030306 microbiology, Microevolution, biology.organism_classification, medicine.disease, Bank vole, Infectious Diseases, microdiversity, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, Puumala virus, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: International audience; In Europe, Puumala virus (PUUV) transmitted by the bank vole (Myodes glareolus) is the causative agent of nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome. In France, very little is known about the spatial and temporal variability of the virus circulating within bank vole populations. The present study involved monitoring of bank vole population dynamics and PUUV microdiversity over a ten-year period (2000–2009) in two forests of the Ardennes region: Elan and Croix-Scaille. Ardennes region is characterised by different environmental conditions associated with different NE epidemiology. Bank vole density and population parameters were estimated using the capture/marking/recapture method, and blood samples were collected to monitor the overall seroprevalence of PUUV in rodent populations. Phylogenetic analyses of fifty-five sequences were performed to illustrate the genetic diversity of PUUV variants between forests. The pattern of the two forests differed clearly. In the Elan forest, the rodent survival was higher, and this limited turn-over resulted in a lower seroprevalence and diversity of PUUV sequences than in the Croix-Scaille forest. Uncovering the links between host dynamics and virus microevolution is improving our understanding of PUUV distribution in rodents and the NE risk.
Published: 2021

4. Universality of cell differentiation trajectories revealed by a reconstruction of transcriptional uncertainty landscapes from single-cell transcriptomic data

Author: Rudiyanto Gunawan, Andras Paldi, Nan Papili Gao, Ulysse Herbach, Olivier Gandrillon, Institute for Chemical and Bioengineering [ETH Zürich] (ICB), Department of Chemistry and Applied Biosciences [ETH Zürich] (D-CHAB), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Multi-scale modelling of cell dynamics : application to hematopoiesis (DRACULA), Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL), Biology, genetics and statistics (BIGS), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY), We also thank the BioSyL Federation and the LabEx Ecofect (ANR-11-LABX-0048) of the University of Lyon for inspiring scientific events., This work was supported by the Swiss National Science Foundation (grant number 157154 and 176279), This work was supported by the ANR research grant SinCity (grant number ANR-17-CE12-0031-01)., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-17-CE12-0031,SinCity,Analyses transcriptomiques sur cellules uniques dont la généalogie est identifiée au cours d'un processus de différentiation(2017), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan (ICJ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Herbach, Ulysse, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, Analyses transcriptomiques sur cellules uniques dont la généalogie est identifiée au cours d'un processus de différentiation - - SinCity2017 - ANR-17-CE12-0031 - AAPG2017 - VALID, and Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan [Villeurbanne] (ICJ)
Subjects: Lineage (genetic), Cellular differentiation, Cell, Computational biology, Cell lineage, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene expression, medicine, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Epigenetics, 030304 developmental biology, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Universality (dynamical systems), single cell, cell differentiation, medicine.anatomical_structure, gene expression, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], epigenetic landscape, heterogeneity, 030217 neurology & neurosurgery
Abstract: We employed our previously-described single-cell gene expression analysis CALISTA (Clustering And Lineage Inference in Single-Cell Transcriptional Analysis) to evaluate transcriptional uncertainty at the single-cell level using a stochastic mechanistic model of gene expression. We reconstructed a transcriptional uncertainty landscape during cell differentiation by visualizing single-cell transcriptional uncertainty surface over a two dimensional representation of the single-cell gene expression data. The reconstruction of transcriptional uncertainty landscapes for ten publicly available single-cell gene expression datasets from cell differentiation processes with linear, single or multi-branching cell lineage, reveals universal features in the cell differentiation trajectory that include: (i) a peak in single-cell uncertainty during transition states, and in systems with bifurcating differentiation trajectories, each branching point represents a state of high transcriptional uncertainty; (ii) a positive correlation of transcriptional uncertainty with transcriptional burst size and frequency; (iii) an increase in RNA velocity preceeding the increase in the cell transcriptional uncertainty. Finally, we provided biological interpretations of the universal rise-then-fall profile of the transcriptional uncertainty landscape, including a link with the Waddington’s epigenetic landscape, that is generalizable to every cell differentiation system.
Published: 2021

5. The Inflammasome Components NLRP3 and ASC Act in Concert with IRGM To Rearrange the Golgi Apparatus during Hepatitis C Virus Infection

Author: Daussy, Coralie, Monard, Sarah, Guy, Coralie, Muñoz-González, Sara, Chazal, Maxime, Anthonsen, Marit, Jouvenet, Nolwenn, Henry, Thomas, Dreux, Marlène, Meurs, Eliane, Hansen, Marianne Doré, Hépacivirus et Immunité innée, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Signalisation antivirale - Virus sensing and signaling, Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Département de Virologie - Department of Virology, Institut Pasteur [Paris], Inflammasome, Infections bactériennes et autoinflammation, Inflammasome, Bacterial Infections and Autoinflammation (I2BA), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Trafic Vésiculaire, Réponse Innée et Virus – Vesicular trafficking, Innate response, Virus, mmunité innée et trafic vésiculaire - Vesicular trafficking, innate response and viruses (VIV), St. Olavs Hospital HF (St. Olav's University Hospital), This work was supported by grants from the Liaison Committee for Education, Research and Innovation in Central Norway to M.D.H., Agence Nationale pour la Recherche contre le SIDA et les Hépatites Virales (ANRS) to E.F.M., C.F.D., and M.D., and Agence Nationale pour la Recherche (ANR-JCJC) and LabEx Ecofect grant ANR-11-LABX-0048 to M.D., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), CHAZAL, MAXIME, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: MESH: GTP-Binding Proteins, Inflammasomes, [SDV]Life Sciences [q-bio], Golgi Apparatus, Apoptosis, Golgi rearrangement, Hepacivirus, ASC, MESH: Golgi Apparatus, MESH: Inflammasomes, NLRP3, GTP-Binding Proteins, NLR Family, Pyrin Domain-Containing 3 Protein, Humans, MESH: Hepacivirus, ZIKV, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Hepatitis C, MESH: Humans, MESH: Apoptosis, IRGM, Hepatitis C, Virus-Cell Interactions, CARD Signaling Adaptor Proteins, MESH: NLR Family, Pyrin Domain-Containing 3 Protein, HCV, MESH: CARD Signaling Adaptor Proteins, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Abstract: Numerous pathogens can affect cellular homeostasis and organelle dynamics. Hepatitis C virus (HCV) triggers Golgi fragmentation through the immunity-related GTPase M (IRGM), a resident Golgi protein, to enhance its lipid supply for replication., Hepatitis C virus (HCV) infection triggers Golgi fragmentation through the Golgi-resident protein immunity-related GTPase M (IRGM). Here, we report the roles of NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) and ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain [CARD]), two inflammasome components, in the initial events leading to this fragmentation. We show that ASC resides at the Golgi with IRGM at homeostasis. Upon infection, ASC dissociates from both IRGM and the Golgi and associates with HCV-induced NLRP3. NLRP3 silencing inhibits Golgi fragmentation. ASC silencing disrupts the Golgi structure in both control and infected cells and reduces the localization of IRGM at the Golgi. IRGM depletion in the ASC-silenced cells cannot totally restore the Golgi structure. These data highlight a role for ASC, upstream of the formation of the inflammasome, in regulating IRGM through its control on the Golgi. A similar mechanism occurs in response to nigericin treatment, but not in cells infected with another member of the Flaviviridae family, Zika virus (ZIKV). We propose a model for a newly ascribed function of the inflammasome components in Golgi structural remodeling during certain stimuli. IMPORTANCE Numerous pathogens can affect cellular homeostasis and organelle dynamics. Hepatitis C virus (HCV) triggers Golgi fragmentation through the immunity-related GTPase M (IRGM), a resident Golgi protein, to enhance its lipid supply for replication. Here, we reveal the role of the inflammasome components NLRP3 and ASC in this process, thus uncovering a new interplay between effectors of inflammation and viral infection or stress. We show that the inflammasome component ASC resides at the Golgi under homeostasis and associates with IRGM. Upon HCV infection, ASC is recruited to NLRP3 and dissociates from IRGM, causing Golgi fragmentation. Our results uncover that aside from their known function in the inflammation response, these host defense regulators also ensure the maintenance of intact intracellular structure in homeostasis, while their activation relieves factors leading to Golgi remodeling.
Published: 2021

6. HDV-Like Viruses

Author: Stéphanie Jacquet, Jimena Pérez-Vargas, Dominique Pontier, François-Loïc Cosset, Natalia Freitas, Rémi Pereira de Oliveira, Référent HAL, CIRI, IDEXLYON - - IDEXLYON2016 - ANR-16-IDEX-0005 - IDEX - VALID, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID, Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), The laboratory of François-Loïc Cosset is supported by the Agence Nationale de la Recherche sur le SIDA et les Hépatites Virales | Maladies Infectieuses Emergentes (ANRS | MIE), the IDEXLYON (ANR-16-IDEX-0005) and the LabEx Ecofect (ANR-11-LABX-0048) of the 'Université de Lyon'(http://ecofect.universite-lyon.fr/, accessed on 25 April 2021), within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007) operated by the ANR., ANR-16-IDEX-0005,IDEXLYON,IDEXLYON(2016), ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Hepatitis C virus, viruses, [SDV]Life Sciences [q-bio], Review, Genome, Viral, Biology, medicine.disease_cause, Virus Replication, Microbiology, Virus, Host Specificity, Dengue fever, Evolution, Molecular, 03 medical and health sciences, Viral Proteins, Viral envelope, Virology, evolution, medicine, origin, Animals, Humans, helper virus, Phylogeny, 030304 developmental biology, Hepatitis B virus, 0303 health sciences, 030306 microbiology, virus diseases, biochemical phenomena, metabolism, and nutrition, medicine.disease, QR1-502, Hepatitis D, 3. Good health, HDV-like viruses, [SDV] Life Sciences [q-bio], Infectious Diseases, Novel virus, Helper virus, Human Virus, Hepatitis Delta Virus, Helper Viruses
Abstract: International audience; Hepatitis delta virus (HDV) is a defective human virus that lacks the ability to produce its own envelope proteins and is thus dependent on the presence of a helper virus, which provides its surface proteins to produce infectious particles. Hepatitis B virus (HBV) was so far thought to be the only helper virus described to be associated with HDV. However, recent studies showed that divergent HDV-like viruses could be detected in fishes, birds, amphibians, and invertebrates, without evidence of any HBV-like agent supporting infection. Another recent study demonstrated that HDV can be transmitted and propagated in experimental infections ex vivo and in vivo by different enveloped viruses unrelated to HBV, including hepatitis C virus (HCV) and flaviviruses such as Dengue and West Nile virus. All this new evidence, in addition to the identification of novel virus species within a large range of hosts in absence of HBV, suggests that deltaviruses may take advantage of a large spectrum of helper viruses and raises questions about HDV origins and evolution.
Published: 2021

7. Reprogrammed Pteropus Bat Stem Cells as A Model to Study Host-Pathogen Interaction during Henipavirus Infection

Author: Aurine, Noémie, Baquerre, Camille, Gaudino, Maria, Jean, Christian, Dumont, Claire, Rival-Gervier, Sylvie, Kress, Clémence, Horvat, Branka, Pain, Bertrand, PAIN, Bertrand, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Structure et fonctions de la protéine C du virus Nipah - - NiPah-C2018 - ANR-18-CE11-0014 - AAPG2018 - VALID, Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (U1208 Inserm - UCBL1 / SBRI - USC 1361 INRAE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The study was supported by LABEX ECOFECT (ANR-11-LABX-0048) of Lyon University, within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007), operated by the French National Research Agency (ANR), and by ANR-18-CE11-0014, by grants from the 'Finovi Foundation' (AO13) and Aviesan Sino-French agreement on Nipah virus study., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), ANR-18-CE11-0014,NiPah-C,Structure et fonctions de la protéine C du virus Nipah(2018), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The study was supported by LABEX ECOFECT (ANR-11-LABX-0048) of Lyon University, within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007), operated by the French National Research Agency (ANR), and by ANR-18-CE11-0014-02, by grants from the 'Finovi Foundation' (AO13) and Aviesan Sino-French agreement on Nipah virus study., and Rival-Gervier, Sylvie
Subjects: [SDV.BA] Life Sciences [q-bio]/Animal biology, [SDV.IMM] Life Sciences [q-bio]/Immunology, QH301-705.5, [SDV.BA]Life Sciences [q-bio]/Animal biology, [SDV]Life Sciences [q-bio], Henipavirus, bats, interferon-stimulated gene, reprogramming, Nipah virus, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Article, [SDV] Life Sciences [q-bio], stem cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, Biology (General), emerging infection, innate immunity, transcriptome, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract: The data sets are available in GSE134585 datasets.; International audience; Bats are natural hosts for numerous zoonotic viruses, including henipaviruses, which are highly pathogenic for humans, livestock, and other mammals but do not induce clinical disease in bats. Pteropus bats are identified as a reservoir of henipaviruses and the source of transmission of the infection to humans over the past 20 years. A better understanding of the molecular and cellular mechanisms allowing bats to control viral infections requires the development of relevant, stable, and permissive cellular experimental models. By applying a somatic reprogramming protocol to Pteropus bat primary cells, using a combination of ESRRB (Estrogen Related Receptor Beta), CDX2 (Caudal type Homeobox 2), and c-MYC (MYC proto-oncogene) transcription factors, we generated bat reprogrammed cells. These cells exhibit stem cell-like characteristics and neural stem cell molecular signature. In contrast to primary fibroblastic cells, these reprogrammed stem cells are highly permissive to henipaviruses and exhibit specific transcriptomic profiles with the particular expression of certain susceptibility factors such as interferon-stimulated genes (ISG), which may be related to viral infection. These Pteropus bat reprogrammed stem cells should represent an important experimental tool to decipher interactions during henipaviruses infection in Pteropus bats, facilitate isolation and production of bat-borne viruses, and to better understand the bat biology.
Published: 2021

8. The interplays between Crimean-Congo hemorrhagic fever virus (CCHFV) M segment-encoded accessory proteins and structural proteins promote virus assembly and infectivity

Author: Natalia Freitas, Friedemann Weber, Solène Lerolle, François-Loïc Cosset, Gregory Neveu, Solène Denolly, Vincent Legros, Camille Lévy, Margot Enguehard, Eric Bergeron, Stephanie Devignot, Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Justus-Liebig-Universität Gießen (JLU), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Université de Lyon, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), This work performed in the laboratory of FLC was supported by the French National Research Agency (ANR), the IDEXLYON (ANR-16-IDEX-0005) and the LabEx Ecofect (ANR-11-LABX-0048) of the 'Université de Lyon' (http://ecofect.universite-lyon.fr/), within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007) operated by the ANR. VL received financial support from the 'IDEXLYON IMPULSION 2019' project (ANR-16-IDEX-0005) of the ‘‘Université de Lyon', within the program ‘‘Investissements d’Avenir' (ANR-16-IDEX-0005) and from the 'Global Health Impulsion 2020' project of VetAgro Sup. FW is supported by the CCHVaccine consortium that has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 732732, and by the Swedish Research Council (Vetenskapsrådet, VR) section Research Environment, Infection Biology (contract number 2018-05766)., ANR-16-IDEX-0005,IDEXLYON,IDEXLYON(2016), ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Bodescot, Myriam, IDEXLYON - - IDEXLYON2016 - ANR-16-IDEX-0005 - IDEX - VALID, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cell Membranes, Glycobiology, Golgi Apparatus, Biochemistry, Virions, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Biology (General), chemistry.chemical_classification, Infectivity, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Secretory Pathway, 030302 biochemistry & molecular biology, 3. Good health, Transport protein, Protein Transport, Cell Processes, Hemorrhagic Fever Virus, Crimean-Congo, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, symbols, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cellular Structures and Organelles, Research Article, QH301-705.5, Immunology, Biology, Viral Structure, Transfection, Research and Analysis Methods, Microbiology, Virus, 03 medical and health sciences, symbols.namesake, Virology, Cell Line, Tumor, Genetics, Humans, Molecular Biology Techniques, Molecular Biology, Secretory pathway, 030304 developmental biology, Glycoproteins, Viral Structural Proteins, Virus Assembly, Biology and Life Sciences, Membrane Proteins, Protein Secretion, Proteins, Cell Biology, Golgi apparatus, RC581-607, Secretory protein, chemistry, Membrane protein, Parasitology, Immunologic diseases. Allergy, Glycoprotein, Gene Deletion
Abstract: Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne orthonairovirus that has become a serious threat to the public health. CCHFV has a single-stranded, tripartite RNA genome composed of L, M, and S segments. Cleavage of the M polyprotein precursor generates the two envelope glycoproteins (GPs) as well as three secreted nonstructural proteins GP38 and GP85 or GP160, representing GP38 only or GP38 linked to a mucin-like protein (MLD), and a double-membrane-spanning protein called NSm. Here, we examined the relevance of each M-segment non-structural proteins in virus assembly, egress and infectivity using a well-established CCHFV virus-like-particle system (tc-VLP). Deletion of MLD protein had no impact on infectivity although it reduced by 60% incorporation of GPs into particles. Additional deletion of GP38 abolished production of infectious tc-VLPs. The loss of infectivity was associated with impaired Gc maturation and exclusion from the Golgi, showing that Gn is not sufficient to target CCHFV GPs to the site of assembly. Consistent with this, efficient complementation was achieved in cells expressing MLD-GP38 in trans with increased levels of preGc to Gc conversion, co-targeting to the Golgi, resulting in particle incorporation and restored infectivity. Contrastingly, a MLD-GP38 variant retained in the ER allowed preGc cleavage but failed to rescue miss-localization or infectivity. NSm deletion, conversely, did not affect trafficking of Gc but interfered with Gc processing, particle formation and secretion. NSm expression affected N-glycosylation of different viral proteins most likely due to increased speed of trafficking through the secretory pathway. This highlights a potential role of NSm in overcoming Golgi retention and facilitating CCHFV egress. Thus, deletions of GP38 or NSm demonstrate their important role on CCHFV particle production and infectivity. GP85 is an essential viral factor for preGc cleavage, trafficking and Gc incorporation into particles, whereas NSm protein is involved in CCHFV assembly and virion secretion., Author summary Orthonairoviruses, like the lethal Crimean-Congo hemorrhagic fever virus (CCHFV), encode secreted glycoproteins, such as GP38, in addition to virion envelope glycoproteins (Gn and Gc) that are processed by internal cleavage of the viral M segment encoded polyprotein. CCHFV MLD-GP38 proteins (GP160/GP85) also include an N-terminal domain encompassing a mucin-like protein that is released from GP38 by Furin. The protective effect of non-neutralizing monoclonal antibodies targeting GP38 against lethal CCHFV challenge previously highlighted the importance of GP38 in CCHFV replication. CCHFV also encodes a double-membrane-spanning protein (NSm) of unknown function, located between the Gn and Gc on the polyprotein. To investigate the roles of these so-called accessory proteins encoded by the CCHFV M-segment in virus formation and infectivity, we generated several M-segment deletion mutants and tested them in a CCHFV transcription-entry-competent virus-like particle (tc-VLP) system. Here, we demonstrate that GP38 is crucial for Gc biogenesis, interaction with Gn and trafficking to the Golgi, and that its deletion abrogates formation of infectious particles. We also show that NSm increases the rate of protein trafficking through the secretory pathway with altered N-glycosylation profiles that are advantageous for efficient virus release. These data advanced our understanding of GP38 and NSm roles and CCHFV-host interactions.
Published: 2020

9. High Pathogenicity of Nipah Virus from Pteropus lylei Fruit Bats, Cambodia

Author: Julien Fouret, Olivier Reynard, Marion Ferren, Cyrille Mathieu, Claire Dumont, Maria Gaudino, Viktor E. Volchkov, Marie Claude Georges-Courbot, Catherine Legras-Lachuer, Branka Horvat, Noémie Aurine, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Viroscan3D SAS [Lyon, France], Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], This work was supported by LABEX ECOFECT (ANR-11-LABX-0048) of Lyon University, within the program Investissements d'Avenir (ANR-11-IDEX-0007) operated by the French National Research Agency, ANR-18-CE11-0014-02, Aviesan Sino-French Agreement on Nipah Virus Study, and the International Division of the Pasteur Institut in Paris (Actions Concertées Inter-Pasteurienne). J.F. was supported by the doctoral fellowship CIFRE-Défense operated by the Direction Générale de l’Armement., We thank Jean-Marc Reynes and Pasteur Institut staff for providing us with the NiV Cambodia isolate and Doris Preininger, Anton Weissenbacher, and Tiergarten Schönbrunn for P. giganteus bat sampling. We thank Amelia Charlotte Coggon for English proofreading of the manuscript, and we also thank François Enchéry, Kévin Dhondt, Mathieu Iampietro, Sylvain Baize, and Géraldine Gourru-Lesimple for help initiating and finalizing this work., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2012), Mathieu, Cyrille, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Structure et fonctions de la protéine C du virus Nipah - - NiPah-C2018 - ANR-18-CE11-0014 - AAPG2018 - VALID, Immunobiologie des infections virales – Immunobiology of Viral Infections (IbIV), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Bases moléculaires de la pathogénicité virale – Molecular Basis of Viral Pathogenicity (BMPV), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), This work was supported by LABEX ECOFECT (ANR-11-LABX-0048) of Lyon University, within the program Investissements d’Avenir (ANR-11-IDEX-0007) operated by the French National Research Agency, ANR-18-CE11-0014-02, Aviesan Sino-French Agreement on Nipah Virus Study, and the International Division of the Institut Pasteur in Paris (Actions Concertées Inter-Pasteurienne). J.F. was supported by the doctoral fellowship CIFRE-Défense operated by the Direction Générale de l’Armement., ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), ANR-18-CE11-0014,NiPah-C,Structure et fonctions de la protéine C du virus Nipah(2018), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)
Subjects: Permissiveness, Epidemiology, lcsh:Medicine, Nipah virus, Pteropus lylei, Pteropus bats, 0302 clinical medicine, Chiroptera, Genotype, pathogenicity, 030212 general & internal medicine, Phylogeny, CSUR381, Henipavirus Infections, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, fruit bats, Phylogenetic tree, biology, sequencing, High Pathogenicity of Nipah Virus from Pteropus lylei Fruit Bats, Cambodia, phosphoprotein, 3. Good health, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, Cambodia, Henipavirus, Microbiology (medical), henipavirus, spillover, 030231 tropical medicine, Genome, Viral, Real-Time Polymerase Chain Reaction, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Phylogenetics, Animals, Humans, lcsh:RC109-216, viruses, emerging infection, Whole genome sequencing, Whole Genome Sequencing, Research, phylogenetic analysis, animal model, lcsh:R, Outbreak, biology.organism_classification, Virology, zoonoses, hamster, NiV-Malaysia genotype
Abstract: International audience; We conducted an in-depth characterization of the Nipah virus (NiV) isolate previously obtained from a Pteropus lylei bat in Cambodia in 2003 (CSUR381). We performed full-genome sequencing and phylogenetic analyses and confirmed CSUR381 is part of the NiV-Malaysia genotype. In vitro studies revealed similar cell permissiveness and replication of CSUR381 (compared with 2 other NiV isolates) in both bat and human cell lines. Sequence alignments indicated conservation of the ephrin-B2 and ephrin-B3 receptor binding sites, the glycosylation site on the G attachment protein, as well as the editing site in phosphoprotein, suggesting production of nonstructural proteins V and W, known to counteract the host innate immunity. In the hamster animal model, CSUR381 induced lethal infections. Altogether, these data suggest that the Cambodia bat-derived NiV isolate has high pathogenic potential and, thus, provide insight for further studies and better risk assessment for future NiV outbreaks in Southeast Asia.
Published: 2020

10. Demographic fluctuation of community-acquired antibiotic-resistant Staphylococcus aureus lineages: potential role of flimsy antibiotic exposure

Author: Binh An Diep, Typhanie Le Hir, Paal Skytt Andersen, Claude-Alexandre Gustave, Marc Stegger, Anne-Catrin Uhlemann, Thierry Wirth, Yvonne Benito, Philippe Glaser, Patricia Martins-Simões, Michèle Bes, François Vandenesch, Anne Tristan, Frédéric Laurent, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Reference des Staphylocoques, Université de Lyon, Statens Serum Institut [Copenhagen], Department of Medicine [San Francisco], University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Columbia University Irving Medical Center (CUIMC), Ecologie et Evolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Université Paris-Sud - Paris 11 (UP11)-Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), This work was performed within the framework of the LABEX ECOFECT (ANR-11-LABX-0048) of Université de Lyon, within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR)., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UCSF), University of California-University of California, Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Sud Orsay-Centre National de la Recherche Scientifique (CNRS), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Davoine, Laure-Hélène, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Sud Orsay-Centre National de la Recherche Scientifique (CNRS)
Subjects: Methicillin-Resistant Staphylococcus aureus, 0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, Virulence Factors, medicine.drug_class, Fusidic acid, 030106 microbiology, Antibiotics, Biology, Staphylococcal infections, medicine.disease_cause, Microbiology, Article, Middle East, 03 medical and health sciences, Antibiotic resistance, Africa, Northern, Effective population size, Drug Resistance, Fungal, medicine, Animals, Humans, Pathogen, Ecology, Evolution, Behavior and Systematics, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Staphylococcal Infections, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Methicillin-resistant Staphylococcus aureus, 3. Good health, Europe, 030104 developmental biology, Staphylococcus aureus, Biofilms, North America, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, medicine.drug
Abstract: International audience; Community-acquired (CA)-~as opposed to hospital acquired- methicillin-resistant Staphylococcus aureus (MRSA) lineages arose worldwide during the 1990s. To determine which factors, including selective antibiotic pressure, govern the expansion of two major lineages of CA-MRSA, namely "USA300" in Northern America and "European ST80" in North Africa, Europe and Middle-East, we explored virulence factor expression, and fitness levels with or without antibiotics. The sampled strains were collected in a temporal window representing various steps of the epidemics, reflecting predicted changes in effective population size as inferred from whole-genome analysis. In addition to slight variations in virulence factor expression and biofilm production that might influence the ecological niches of theses lineages, competitive fitness experiments revealed that the biological cost of resistance to methicillin, fusidic acid and fluoroquinolones is totally reversed in the presence of trace amount of antibiotics. Our results suggest that low-level antibiotics exposure in human and animal environments contributed to the expansion of both European ST80 and USA300 lineages in community settings. This surge was likely driven by antibiotic (ab)use promoting the accumulation of antibiotics as environmental pollutants. The current results provide a novel link between effective population size increase of a pathogen and a selective advantage conferred by antibiotic resistance.
Published: 2018

11. Regulation of measles virus gene expression by P protein coiled-coil properties

Author: Louis-Marie, Bloyet, Antoine, Schramm, Carine, Lazert, Bertrand, Raynal, Maggy, Hologne, Olivier, Walker, Sonia, Longhi, Denis, Gerlier, Immunobiologie des infections virales – Immunobiology of Viral Infections, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Biophysique Moléculaire (Plate-forme), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Biophysics of complex systems, Institut des Sciences Analytiques (ISA), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), This work was supported, in part, by French ANR NITRODEP (project ANR-13-PDOC-0010-01) (www.agence-nationale-recherche.fr) and LABEX ECOFECT (ANR-11-LABX-0048) of Lyon University, within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR). The studies described here were carried out with the financial support of the CNRS.A.S. is a recipient of a Ph.D. fellowship from the French Ministry of National Education, Research and Technology allotted to the Ecole Doctorale des Sciences de la Vie et de la Santé (Aix-Marseille Université)., ANR-13-PDOC-0010,NITRODEP,Nouvelle exploration du tropisme et de la dissémination des Paramyxoviridae encephalitogènes(2013), ANR-11-IDEX-0007-02/11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), Immunobiologie des infections virales – Immunobiology of Viral Infections (IbIV), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bussy, Agnès, Retour Post-Doctorant - Nouvelle exploration du tropisme et de la dissémination des Paramyxoviridae encephalitogènes - - NITRODEP2013 - ANR-13-PDOC-0010 - PDOC - VALID, and Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID
Subjects: Gene Expression Regulation, Viral, Protein Conformation, alpha-Helical, Protein Folding, Molecular Dynamics Simulation, Viral Proteins, Protein Domains, Virology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, RNA, Small Interfering, Research Articles, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Binding Sites, SciAdv r-articles, Phosphoproteins, Recombinant Proteins, HEK293 Cells, Measles virus, Mutagenesis, Paramyxoviridae, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, lipids (amino acids, peptides, and proteins), RNA Interference, Protein Multimerization, Research Article
Abstract: Measles virus gene expression requires a precise range of cohesiveness and a kink in the coiled coil of its phosphoprotein., The polymerase of negative-stranded RNA viruses consists of the large protein (L) and the phosphoprotein (P), the latter serving both as a chaperon and a cofactor for L. We mapped within measles virus (MeV) P the regions responsible for binding and stabilizing L and showed that the coiled-coil multimerization domain (MD) of P is required for gene expression. MeV MD is kinked as a result of the presence of a stammer. Both restoration of the heptad regularity and displacement of the stammer strongly decrease or abrogate activity in a minigenome assay. By contrast, P activity is rather tolerant of substitutions within the stammer. Single substitutions at the “a” or “d” hydrophobic anchor positions with residues of variable hydrophobicity revealed that P functionality requires a narrow range of cohesiveness of its MD. Results collectively indicate that, beyond merely ensuring P oligomerization, the MD finely tunes viral gene expression through its cohesiveness.
Published: 2019

12. Sensing of cell-associated HTLV by plasmacytoid dendritic cells is regulated by dense β-galactoside glycosylation

Author: Assil, Sonia, Futsch, Nicolas, Décembre, Elodie, Alais, Sandrine, Gessain, Antoine, François-Loïc, Cosset, Mahieux, Renaud, Dreux, Marlène, Dutartre, Hélène, Bodescot, Myriam, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), This work was supported by 'Ligue Nationale contre le Cancer, équipe labélisée program' EL2013-3Mahieux to Dr Hélène Dutartre and Pr Renaud Mahieux, by ‘‘Agence Nationale pour la Recherche’’ (ANR-JCJC-EXAMIN), ‘‘Agence Nationale pour la Recherche contre le SIDA et les Hépatites Virales’’ (ANRS-AO 2016-01) and LabEx Ecofect (ANR-11-LABX-0048) of the 'Université de Lyon', within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007) to Dr Marlène Dreux, and by LabEx Ecofect (ANR-11-LABX-0048) of the 'Université de Lyon', within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007) to Dr François-Loïc Cosset. Sonia Assil’s PhD fellowship was sponsored by the French ministry and the 'Ligue contre le Cancer'. Nicolas Futsch’s PhD fellowship was sponsored by the 'Ligue contre le Cancer'., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
Subjects: RNA viruses, Glycosylation, viruses, T-Lymphocytes, Glycobiology, Pathology and Laboratory Medicine, Biochemistry, Jurkat Cells, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Lectins, Medicine and Health Sciences, Biology (General), Post-Translational Modification, Staining, Human T-lymphotropic virus 1, Human T-lymphotropic virus 2, Cell Staining, Drugs, hemic and immune systems, Medical Microbiology, Viral Pathogens, Interferon Type I, Viruses, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, Pathogens, Research Article, Cell Binding, Cell Physiology, [SDV.IMM] Life Sciences [q-bio]/Immunology, QH301-705.5, Viral Structure, Research and Analysis Methods, Microbiology, Virology, Retroviruses, Humans, Microbial Pathogens, Pharmacology, Biology and life sciences, Heparin, Organisms, Interferon-alpha, Proteins, Galactosides, Dendritic Cells, Htlv-1, Cell Biology, RC581-607, HTLV-I Infections, Immunity, Innate, Specimen Preparation and Treatment, Immunologic diseases. Allergy, Viral Transmission and Infection
Abstract: Human T Lymphotropic virus (HTLV) infection can persist in individuals resulting, at least in part, from viral escape of the innate immunity, including inhibition of type I interferon response in infected T-cells. Plasmacytoid dendritic cells (pDCs) are known to bypass viral escape by their robust type I interferon production. Here, we demonstrated that pDCs produce type I interferons upon physical cell contact with HTLV-infected cells, yet pDC activation inversely correlates with the ability of the HTLV-producing cells to transmit infection. We show that pDCs sense surface associated-HTLV present with glycan-rich structure referred to as biofilm-like structure, which thus represents a newly described viral structure triggering the antiviral response by pDCs. Consistently, heparan sulfate proteoglycans and especially the cell surface pattern of terminal β-galactoside glycosylation, modulate the transmission of the immunostimulatory RNA to pDCs. Altogether, our results uncover a function of virus-containing cell surface-associated glycosylated structures in the activation of innate immunity., Author summary Human T Lymphotropic virus type (HTLV) establishes persistent infections, leading to adult T-cell Leukemia, a life-threatening cancer in chronically-infected individuals. Viral persistence likely results from a failure of immune responses to eradicate viral replication, a least in part, by viral escape from innate immunity, and notably via decreased production of type I interferons (IFN-I) by infected cells. Plasmacytoid dendritic cells (pDCs) are known as robust producers of IFN-I in response to virus stimulation, thus bypassing the viral mechanisms to evade pathogen-sensing pathways in infected cells. However, HTLV particles are not detected in biological fluids of infected individuals, raising the question of the pDC-activating signal. Here, we demonstrate that pDCs produce IFN-I upon physical contacts with HTLV-infected cells. We show that pDCs sense surface associated-HTLV present with glycan-rich structure, referred to as HTLV-biofilm-like structure. Importantly, the sensing of infected cells by pDCs is modulated by the glycosylation pattern at the surface of infected cells. This newly ascribed regulation of innate immunity activation by cell surface-associated glycans might contribute to the differential activation levels of antiviral response to infected cells when their glycosylation profile is modified, such as for chronically infected cells or tumor cells.
Published: 2018

13. Plasmacytoid dendritic cells control dengue and Chikungunya virus infections via IRF7-regulated interferon responses

Author: Brian Webster, Scott W Werneke, Biljana Zafirova, Sébastien This, Séverin Coléon, Elodie Décembre, Helena Paidassi, Isabelle Bouvier, Pierre-Emmanuel Joubert, Darragh Duffy, Thierry Walzer, Matthew L Albert, Marlène Dreux, Trafic Vésiculaire, Réponse Innée et Virus – Vesicular trafficking, Innate response, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Genentech, Inc. [San Francisco], Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases, This work was supported by grants from the ‘Agence Nationale pour la Recherche’ (ANR-JCJC-EXAMIN), the ‘‘Agence Nationale pour la Recherche contre le SIDA et les Hépatites Virales’’ (ANRS-AO 2016–01) and the LabEx Ecofect Grant ANR-11-LABX-0048 to MD, ANR-14-CE14-0015-02 CHIKV-Viro-Immuno to MLA. BW’s postdoctoral fellowship was sponsored by EMBO (ALTF 1466–2014). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, We thank A Davidson (Bristol University) for providing the DENV-2 strain New Guinea C, P Despres (Pasteur Institut, Paris, France) for the anti-E DENV 3H5 antibody, V Lotteau (CIRI, Lyon, France) for Influenza A virus stocks, FV Chisari (Scripps Research Institute, La Jolla, CA) for the Huh-7.5.1 cells, T Taniguchi (University of Tokyo, Tokyo, Japan) for the Irf3/7 DKO mice, J Tschopp for the cardif-/- mice, and S Akira for the Tlr7-/- mice. We are grateful to Y Jaillais for critical reading of the manuscript, F Fusil for assistance with mice and to our colleagues for encouragement and help. We acknowledge the contribution of SFR Biosciences (UMS3444/CNRS, US8/Inserm, ENS de Lyon, UCBL) facilities, PBES and cytometry for mice housing and technical assistance., ANR-13-JSV3-0004,EXAMIN,Les Exosomes enrichis en ARN viraux sont Médiateurs de la réponse Interféron(2013), ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vougny, Marie-Christine, Jeunes Chercheuses et Jeunes Chercheurs - Les Exosomes enrichis en ARN viraux sont Médiateurs de la réponse Interféron - - EXAMIN2013 - ANR-13-JSV3-0004 - JC - VALID, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, and Appel à projets générique - Multiplication et Relation avec l'hôte du virus Chikungunya - - CHIKV-Viro-Immuno2014 - ANR-14-CE14-0015 - Appel à projets générique - VALID
Subjects: Male, [SDV.IMM] Life Sciences [q-bio]/Immunology, QH301-705.5, Science, Interferon Regulatory Factor-7, viruses, Dengue, immunology, Interferon-gamma, Mice, Animals, Humans, dendritic cells, human, Biology (General), mouse, Mice, Knockout, virus diseases, hemic and immune systems, Dengue Virus, Survival Analysis, virology, Killer Cells, Natural, Mice, Inbred C57BL, interferons, Disease Models, Animal, Gene Expression Regulation, inflammation, Host-Pathogen Interactions, Interferon Type I, Medicine, Chikungunya Fever, RNA, Viral, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Interferon Regulatory Factor-3, Chikungunya virus, Spleen, Signal Transduction
Abstract: International audience; Type I interferon (IFN-I) responses are critical for the control of RNA virus infections, however, many viruses, including Dengue (DENV) and Chikungunya (CHIKV) virus, do not directly activate plasmacytoid dendritic cells (pDCs), robust IFN-I producing cells. Herein, we demonstrated that DENV and CHIKV infected cells are sensed by pDCs, indirectly, resulting in selective IRF7 activation and IFN-I production, in the absence of other inflammatory cytokine responses. To elucidate pDC immunomodulatory functions, we developed a mouse model in which IRF7 signaling is restricted to pDC. Despite undetectable levels of IFN-I protein, pDC-restricted IRF7 signaling controlled both viruses and was sufficient to protect mice from lethal CHIKV infection. Early pDC IRF7-signaling resulted in amplification of downstream antiviral responses, including an accelerated natural killer (NK) cell-mediated type II IFN response. These studies revealed the dominant, yet indirect role of pDC IRF7-signaling in directing both type I and II IFN responses during arbovirus infections.
Published: 2018

14. Age and spatio-temporal variations in food resources modulate stress-immunity relationships in three populations of wild roe deer

Author: Jeffrey Carbillet, Marine Hollain, Benjamin Rey, Rupert Palme, Maryline Pellerin, Corinne Regis, Anne Geffré, Jeanne Duhayer, Sylvia Pardonnet, François Debias, Joël Merlet, Jean-François Lemaître, Hélène Verheyden, Emmanuelle Gilot-Fromont, Unité de recherche Comportement et Ecologie de la Faune Sauvage (CEFS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), LTSER ZA PYRenees GARonne, Centre National de la Recherche Scientifique (CNRS), Institute of Ecology and Earth Sciences [Tartu], University of Tartu, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Office français de la biodiversité (OFB), University of Veterinary Medicine [Vienna] (Vetmeduni), Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), The study was funded by INRAE, VetAgro Sup and ONCFS/OFB, ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), SEGUIN, Nathalie, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, and PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID
Subjects: Innate immunity, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Hydrocortisone, Deer, Ecophysiology, Stress hormones, Adaptive immunity, Animals, Wild, Trade-off, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, [SDV.GEN.GPO] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Animals, Faecal glucocorticoid metabolites, [SDV.BA.ZV] Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, Animal Science and Zoology, [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Glucocorticoids, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Living in variable and unpredictable environments, organisms face recurrent stressful situations. The endocrine stress response, which includes the secretion of glucocorticoids, helps organisms to cope with these perturbations. Although short-term elevations of glucocorticoid levels are often associated with immediate beneficial consequences for individuals, long-term glucocorticoid elevation can compromise key physiological functions such as immunity. While laboratory works highlighted the immunosuppressive effect of long-term elevated glucocorticoids, it remains largely unknown, especially in wild animals, whether this relationship is modulated by individual and environmental characteristics. In this study, we explored the co-variation between baseline cortisol levels, assessed non-invasively using faecal cortisol metabolites (FCMs), and 12 constitutive indices of innate, inflammatory, and adaptive immune functions, in wild roe deer living in three populations with contrasting environmental conditions. Using longitudinal data on 564 individuals, we further investigated whether age and spatio-temporal variations in the quantity and quality of food resources affect the relationship between FCMs and immunity. Negative covariation with glucocorticoids was evident only for innate and inflammatory markers of immunity, while adaptive immunity appeared to be positively or not linked to glucocorticoids. In addition, the negative covariations were generally exacerbated, or revealed, in individuals facing harsh environmental constraints and in old individuals. Therefore, our results highlight the importance of measuring multiple immune markers of immunity in individuals from contrasted environments to unravel the complex relationships between glucocorticoids and immunity in wild animals. Our results also help explain conflicting results found in the literature and could improve our understanding of the long-term consequences of elevated glucocorticoid levels on disease spread and population dynamics.
Published: 2023

15. Mycobacterium tuberculosis genetic features associated with pulmonary tuberculosis severity

Author: Charlotte Genestet, Guislaine Refrégier, Elisabeth Hodille, Rima Zein-Eddine, Adrien Le Meur, Fiona Hak, Alexia Barbry, Emilie Westeel, Jean-Luc Berland, Astrid Engelmann, Isabelle Verdier, Gérard Lina, Florence Ader, Stéphane Dray, Laurent Jacob, François Massol, Samuel Venner, Oana Dumitrescu, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Institut des Agents Infectieux [Lyon] (IAI), Ecologie Systématique et Evolution (ESE), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Pathogènes Emergents, Fondation Mérieux, Centre Hospitalier Fleyriat [Bourg en Bresse], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Évolution, Écologie et Paléontologie (Evo-Eco-Paleo) - UMR 8198 (Evo-Eco-Paléo (EEP)), Université de Lille-Centre National de la Recherche Scientifique (CNRS), CHU Lille, ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), Massol, François, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Microbiology (medical), Genetic heterogeneity, Genome-wide association study, Infectious Diseases, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Whole genome sequencing, Pulmonary tuberculosis, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, Mycobacterium tuberculosis, Structural equation modeling
Abstract: International audience; Objective: Mycobacterium tuberculosis (Mtb) infections result in a wide spectrum of clinical presentations but without proven Mtb genetic determinants. Herein, we hypothesised that genetic features of Mtb clinical isolates, such as specific polymorphisms or micro-diversity, may be linked to tuberculosis (TB) severity.Methods: 234 pulmonary TB patients (including 193 drug-susceptible and 14 mono-resistant cases diagnosed between 2017 and 2020 and 27 multidrug-resistant cases diagnosed between 2010 and 2020) were stratified according to TB disease severity and Mtb genetic features were explored using whole genome sequencing, including heterologous single nucleotide polymorphism (SNP) calling to explore micro-diversity. Finally, we performed a structural equation modelling (SEM) analysis to relate TB severity to Mtb genetic features.Results: Clinical isolates from patients with mild TB carried mutations in genes associated with host-pathogen interaction, while those from patients with moderate/severe TB carried mutations associated with regulatory mechanisms. Genome-wide association study identified a SNP in the promoter of the gene coding for the virulence regulator EspR statistically associated with moderate/severe disease. SEM and model comparisons indicated that TB severity was associated with the detection of Mtb micro-diversity within clinical isolates and to the espR SNP.Conclusions: Taken together, these results provide a new insight to better understand TB pathophysiology and could provide new prognosis tool for pulmonary TB severity.
Published: 2022

16. Nebulized fusion inhibitory peptide protects cynomolgus macaques from measles virus infection

Author: Olivier Reynard, Claudia Gonzalez, Claire Dumont, Mathieu Iampietro, Marion Ferren, Sandrine Le Guellec, Lajoie Laurie, Cyrille Mathieu, Gabrielle Carpentier, Georges Roseau, Francesca T. Bovier, Yun Zhu, Deborah Le Pennec, Jérome Montharu, Amin Addetia, Alexander L. Greninger, Christopher A. Alabi, Elise Brisebard, Anne Moscona, Laurent Vecellio, Matteo Porotto, Branka Horvat, Reynard, Olivier, Gonzalez, Claudia, Dumont, Claire, Iampietro, Mathieu, Ferren, Marion, Le Guellec, Sandrine, Laurie, Lajoie, Mathieu, Cyrille, Carpentier, Gabrielle, Roseau, George, Bovier, Francesca T, Zhu, Yun, Le Pennec, Deborah, Montharu, Jérome, Addetia, Amin, Greninger, Alexander L, Alabi, Christopher A, Brisebard, Elise, Moscona, Anne, Vecellio, Laurent, Porotto, Matteo, Horvat, Branka, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT), DTF-Aerodrug, DTF, Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Columbia University College of Physicians and Surgeons, Capital University of Medical Sciences [Beijing] (CUMS), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Washington [Seattle], Cornell University [New York], Expertise en Anatomie Pathologique (APEX), Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, France, Region ARA (Pack Ambition Recherche, project AerVirStop-BH), United States Department of Health & Human Services National Institutes of Health (NIH) - USA (NS09126, NS105699, AI159085), ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), ANR-16-ASMA-0008,NebuNipaStop,Nébulisation de peptides anti-viraux pour lutter contre l'infection par le virus Nipah(2016), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chanteloup, Nathalie Katy, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID, Nébulisation de peptides anti-viraux pour lutter contre l'infection par le virus Nipah - - NebuNipaStop2016 - ANR-16-ASMA-0008 - ASTRID-Maturation - VALID, and University of Washington Medical Center
Subjects: General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Animals, Humans, Viral Fusion Protein, Macaca fasciculari, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Multidisciplinary, Animal, SARS-CoV-2, COVID-19, General Chemistry, Macaca fascicularis, Measles virus, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Measles viru, Peptide, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Peptides, Viral Fusion Proteins, Human, Measles
Abstract: Measles is the most contagious airborne viral infection and the leading cause of child death among vaccine-preventable diseases. We show here that aerosolized lipopeptide fusion inhibitors, derived from heptad-repeat regions of the measles virus (MeV) fusion protein, block respiratory MeV infection in a non-human primate model, the cynomolgus macaque. We used a custom-designed mesh nebulizer to ensure efficient aerosol delivery of peptides to the respiratory tract and demonstrated the absence of adverse effects and lung pathology in macaques. The nebulized peptide efficiently prevented MeV infection, resulting in the complete absence of MeV RNA, MeV-infected cells, and MeV-specific humoral responses in treated animals. This strategy provides an additional shield which complements vaccination to fight against respiratory infection, presenting a proof-of-concept for the aerosol delivery of fusion inhibitory peptides to protect against measles and other airborne viruses, including SARS-CoV-2, in case of high-risk exposure, that can be readily translated to human trials.
Published: 2022

17. Co-variation between glucocorticoids, behaviour and immunity supports the pace-of-life syndrome hypothesis: an experimental approach

Author: Rupert Palme, Chloé Monestier, Marie-Line Maublanc, Marine Wasniewski, Benoit Rannou, Guillaume Le Loc’h, Typhaine Lavabre, Emmanuelle Gilot-Fromont, Hélène Verheyden, Luca Börger, Benjamin Rey, Jeffrey Carbillet, Nicolas Cebe, Jean-Luc Rames, Unité de recherche Comportement et Ecologie de la Faune Sauvage (CEFS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), University of Veterinary Medicine [Vienna] (Vetmeduni), University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, Bankiva, Swansea University, Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inovie Vet, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de la rage et de la faune sauvage de Nancy (LRFSN), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), SEGUIN, Nathalie, Marchal-Mauer, Sophie, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID, ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), and Laboratoire de Lyon [ANSES]
Subjects: 0106 biological sciences, Hydrocortisone, [SDV.IMM] Life Sciences [q-bio]/Immunology, animal diseases, Adaptive immunity, Physiology, Inflammation, Animals, Wild, Biology, Stress, 010603 evolutionary biology, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, Cortisol, 03 medical and health sciences, Immune system, Capreolus, Immunity, biology.animal, medicine, Animals, Glucocorticoids, General Environmental Science, 030304 developmental biology, Innate immunity, 0303 health sciences, Innate immune system, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Immunology and Microbiology, Ecology, Deer, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Medicine, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Acquired immune system, Coping style, 3. Good health, Vaccination, Roe deer, bacteria, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, General Agricultural and Biological Sciences
Abstract: The biomedical literature has consistently highlighted that long-term elevation of glucocorticoids might impair immune functions, while short-term elevation might enhance them. In contrast, in wild and free-ranging animals, patterns are less clear. In the present study, we explored the stress-immunity relationship in controlled conditions, taking into account the potential effects of behavioural profiles. Thirteen captive roe deer (Capreolus capreolus) were monitored over an eight-week period encompassing two capture events. We assessed how changes in baseline faecal cortisol metabolite (FCM) concentrations following a standardised capture protocol and vaccination affected changes in thirteen immune parameters of the innate and adaptive immunity, and whether behavioural profiles were linked to changes in baseline FCM levels and immune parameters. We found that individuals showing an increase in baseline FCM levels over time also exhibited an increase in immunity, for both the innate and adaptive immunity and were characterised by more reactive behavioural profiles (as indicated by low activity levels, docility to manipulation and neophilia). Consequently, our results suggest that immunity of large mammals may be influenced by their stress level, but also by their behavioural profiles, as it is predicted by the pace-of-life syndrome hypothesis. Our analysis therefore highlights the need to consider co-variations between behavioural profiles, immunity and stress hormones in order to gain a better understanding of the unexplained among-individual variability in the glucocorticoids-immunity relationships observed in wildlife, as they may be underpinned by different life-history strategies.
Published: 2022

18. Integrating population genetics to define conservation units from the core to the edge of Rhinolophus ferrumequinum western range

Author: Raphaël Leblois, Jean-Baptiste Pons, Ondine Filippi-Codaccioni, Anne Loiseau, Dominique Pontier, Jeanne Duhayer, Fiona Mathews, Maxime Leuchtmann, Sylvain Piry, Sébastien J. Puechmaille, Nathalie Charbonnel, Inazio Garin, Orianne Tournayre, Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Université de Lyon, Nature environment, Partenaires INRAE, Department of Zoology and Animal Cell Biology, Faculty of Science and Technology, University of Sussex, GCMP, CREN, Toulouse, France, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), LABEX CEMEB : ANR-11-IDEX-0007, LABEX ECOFECT : ANR-11-LABX-0048 European Union (EU), DREAL Nouvelle-Aquitaine, Region Auvergne-Rhone-Alpes, Region Bourgogne-Franche-Comte, Region Hauts-de-France, Region Nouvelle-Aquitaine, ANR-16-CE02-0008,GenoSpace,Nouveaux outils statistiques pour l'analyse spatiale des données génétiques(2016), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226
Subjects: 0106 biological sciences, Demographic history, Population, 010603 evolutionary biology, 01 natural sciences, microsatellites, 03 medical and health sciences, Chiroptera, lcsh:QH540-549.5, Biologie animale, IUCN Red List, 14. Life underwater, education, Ecology, Evolution, Behavior and Systematics, connectivity, conservation, demographic inference, population genetics, 030304 developmental biology, Nature and Landscape Conservation, Isolation by distance, Animal biology, 0303 health sciences, education.field_of_study, Near-threatened species, Habitat fragmentation, Ecology, biology, [SDV.BA]Life Sciences [q-bio]/Animal biology, Rhinolophus ferrumequinum, 15. Life on land, biology.organism_classification, Geography, Threatened species, Biological dispersal, lcsh:Ecology
Abstract: The greater horseshoe bat(Rhinolophus ferrumequinum)is among the most widespread bat species in Europe but it has experienced severe declines, especially in Northern Europe. This species is listed Near Threatened in the EuropeanIUCN Red List of Threatened Animalsand it is considered to be highly sensitive to human activities and particularly to habitat fragmentation. Therefore, understanding the population boundaries and demographic history of populations of this species is of primary importance to assess relevant conservation strategies. In this study, we used 17 microsatellite markers to assess the genetic diversity, the genetic structure and the demographic history ofR. ferrumequinumcolonies in the Western European part of its distribution. We found high levels of genetic diversity and large population size on the European mainland and lower estimates in England and Northern France. Analyses of clustering and isolation by distance showed a barrier effect of the Channel and potentially of the Mediterranean Sea onR. ferrumequinumbat dispersal. Conversely, we could not reveal any gene flow disruption from both sides of the Western Pyrenees. These results provide important information to improve the delineation ofR. ferrumequinummanagement units in its western range. We suggest that a large management unit corresponding to the European mainland population must be considered. Particular attention should be given to mating territories as they seem to play a key role in maintaining the high levels of genetic mixing between colonies. Smaller management units corresponding to English and Northern France colonies must also be implemented. These insular or peripheral colonies could be at higher risk of extinction in a near future.
Published: 2019

19. Rifampicin exposure reveals within-host Mycobacterium tuberculosis diversity in patients with delayed culture conversion

Author: Sylvain Goutelle, Gerard Lina, Charlotte Genestet, Alexia Barbry, Jonathan Hoffmann, Jean-Luc Berland, Christophe Ginevra, Emilie Westeel, Florence Ader, Elisabeth Hodille, Fabiola Bastian, Samuel Venner, Michel Guichardant, Oana Dumitrescu, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Plateforme DTAMB de biologie moléculaire, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Service des Maladies Infectieuses et Tropicales [Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), ROSSI, Sabine, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Bacterial Diseases, Extensively Drug-Resistant Tuberculosis, Antibiotics, Apoptosis, Drug resistance, Pathology and Laboratory Medicine, White Blood Cells, Medical Conditions, Drug tolerance, Animal Cells, Culture conversion, Medicine and Health Sciences, Biology (General), [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Cell Death, Antimicrobials, Drugs, Bacterial Pathogens, Actinobacteria, Infectious Diseases, Intracellular Pathogens, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Cell Processes, Medical Microbiology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Rifampin, Cellular Types, Pathogens, medicine.drug, Research Article, Tuberculosis, medicine.drug_class, QH301-705.5, Immune Cells, Immunology, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Microbiology, Mycobacterium tuberculosis, 03 medical and health sciences, Virology, Microbial Control, Drug Resistance, Bacterial, Genetics, medicine, Humans, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Molecular Biology, Antibiotics, Antitubercular, Microbial Pathogens, 030304 developmental biology, Pharmacology, Blood Cells, Bacteria, 030306 microbiology, Macrophages, Organisms, Extensively drug-resistant tuberculosis, Biology and Life Sciences, Mycobacteria, Cell Biology, RC581-607, medicine.disease, biology.organism_classification, Tropical Diseases, Parasitology, Immunologic diseases. Allergy, Rifampicin
Abstract: Mycobacterium tuberculosis (Mtb) genetic micro-diversity in clinical isolates may underline mycobacterial adaptation to tuberculosis (TB) infection and provide insights to anti-TB treatment response and emergence of resistance. Herein we followed within-host evolution of Mtb clinical isolates in two cohorts of TB patients, either with delayed Mtb culture conversion (> 2 months), or with fast culture conversion (< 2 months). We captured the genetic diversity of Mtb isolates obtained in each patient, by focusing on minor variants detected as unfixed single nucleotide polymorphisms (SNPs). To unmask antibiotic tolerant sub-populations, we exposed these isolates to rifampicin (RIF) prior to whole genome sequencing (WGS) analysis. Thanks to WGS, we detected at least 1 unfixed SNP within the Mtb isolates for 9/15 patients with delayed culture conversion, and non-synonymous (ns) SNPs for 8/15 patients. Furthermore, RIF exposure revealed 9 additional unfixed nsSNP from 6/15 isolates unlinked to drug resistance. By contrast, in the fast culture conversion cohort, RIF exposure only revealed 2 unfixed nsSNP from 2/20 patients. To better understand the dynamics of Mtb micro-diversity, we investigated the variant composition of a persistent Mtb clinical isolate before and after controlled stress experiments mimicking the course of TB disease. A minor variant, featuring a particular mycocerosates profile, became enriched during both RIF exposure and macrophage infection. The variant was associated with drug tolerance and intracellular persistence, consistent with the pharmacological modeling predicting increased risk of treatment failure. A thorough study of such variants not necessarily linked to canonical drug-resistance, but which are prone to promote anti-TB drug tolerance, may be crucial to prevent the subsequent emergence of resistance. Taken together, the present findings support the further exploration of Mtb micro-diversity as a promising tool to detect patients at risk of poorly responding to anti-TB treatment, ultimately allowing improved and personalized TB management., Author summary Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb), bacteria that are able to persist inside the patient for many months or years, thus requiring long antibiotic treatments. Here we focused on TB patients with delayed response to treatment and we performed genetic characterization of Mtb isolates to search for sub-populations that may tolerate anti-TB drugs. We found that Mtb cultured from 9/15 patients contained different sub-populations, and in vitro drug exposure revealed Mtb sub-populations in 6/15 isolates, none related to known drug-resistance mechanisms. By contrast, drug exposure revealed Mtb sup-populations in 2/20 isolates in the control cohort of patients with fast culture conversion. Furthermore, we characterized a Mtb variant isolated from a sub-population growing in the presence of rifampicin (RIF), a major anti-TB drug. We found that this variant featured a modified lipidic envelope, and that it was able to develop in the presence of RIF and inside human macrophage cells. We performed pharmacological modelling and found that this kind of variant may be related to a poor response to treatment. In conclusion, searching for particular Mtb sub-populations may help to detect patients at risk of treatment failure and provide additional guidance for TB management.
Published: 2021

20. Diverse conjugative elements silence natural transformation in Legionella species

Author: S. Jarraud, Pierre-Alexandre Juan, Kevin Picq, Isabelle Durieux, Laetitia Attaiech, Xavier Charpentier, Christophe Ginevra, Transfert de gène horizontal chez les bactéries pathogènes – Horizontal gene transfer in bacterial pathogens, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre National de Référence des Légionelles (CNR), ANR-17-CE11-0009,RNAchap,Etude d'un nouveau type de chaperonne à ARN(2017), ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), Attaiech, Laetitia, Etude d'un nouveau type de chaperonne à ARN - - RNAchap2017 - ANR-17-CE11-0009 - AAPG2017 - VALID, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Small RNA, Gene Transfer, Horizontal, Bacterial genome size, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Microbiology, natural transformation, Legionella pneumophila, noncoding RNA, 03 medical and health sciences, chemistry.chemical_compound, Plasmid, Bacterial Proteins, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene Silencing, Gene, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Genetics, 0303 health sciences, Multidisciplinary, biology, 030306 microbiology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Biological Sciences, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, DNA-Binding Proteins, Transformation (genetics), chemistry, Horizontal gene transfer, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], horizontal gene transfer, RNA, RNA, Small Untranslated, Transformation, Bacterial, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Mobile genetic elements, conjugative element, DNA, Genome-Wide Association Study, Molecular Chaperones, Plasmids
Abstract: Significance Natural transformation is a major mechanism of horizontal gene transfer. Although the genes required for natural transformation are nearly ubiquitous in bacteria, it is commonly reported that some isolates of transformable species fail to transform. In Legionella pneumophila, we show that the inability of multiple clinical isolates to transform is caused by a conjugative element that shuts down expression of genes required for transformation. Diverse conjugative elements in the Legionella genus have adopted the same inhibition strategy. We propose that inhibition of natural transformation by episomal and integrated conjugative elements can explain the lack of transformability of isolates and also the apparent lack of natural transformation in some species., Natural transformation (i.e., the uptake of DNA and its stable integration in the chromosome) is a major mechanism of horizontal gene transfer in bacteria. Although the vast majority of bacterial genomes carry the genes involved in natural transformation, close relatives of naturally transformable species often appear not competent for natural transformation. In addition, unexplained extensive variations in the natural transformation phenotype have been reported in several species. Here, we addressed this phenomenon by conducting a genome-wide association study (GWAS) on a panel of isolates of the opportunistic pathogen Legionella pneumophila. GWAS revealed that the absence of the transformation phenotype is associated with the conjugative plasmid pLPL. The plasmid inhibits transformation by simultaneously silencing the genes required for DNA uptake and recombination. We identified a small RNA (sRNA), RocRp, as the sole plasmid-encoded factor responsible for the silencing of natural transformation. RocRp is homologous to the highly conserved and chromosome-encoded sRNA RocR which controls the transient expression of the DNA uptake system. Assisted by the ProQ/FinO-domain RNA chaperone RocC, RocRp acts as a substitute of RocR, ensuring that the bacterial host of the conjugative plasmid does not become naturally transformable. Distinct homologs of this plasmid-encoded sRNA are found in diverse conjugative elements in other Legionella species. Their low to high prevalence may result in the lack of transformability of some isolates up to the apparent absence of natural transformation in the species. Generally, our work suggests that conjugative elements obscure the widespread occurrence of natural transformability in bacteria.
Published: 2019

21. Experimental evolution of virulence and associated traits in a Drosophila melanogaster - Wolbachia symbiosis

Author: Caroline Michaud, Hélène Henri, Fabrice Vavre, Emmanuel Desouhant, David Monnin, Manon Villa, Natacha Kremer, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Agence Nationale de la Recherche: ‘ImmunSymbArt’ ANR-2010-BLAN-1701-01 and ‘RESIST’ ANR-16-CE02-0013-01. This work was performed within the framework of the LABEX ECOFECT (ANR-11-LABX-0048) of Université de Lyon, within the programme ‘Investissements d’Avenir’ (ANR-11-IDEX-0007)., ANR-16-CE02-0013,RESIST,Evolution rapide des interactions symbiotiques en réponse au stress : processus et mécanismes(2016), ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), and ANR-10-BLAN-1701,ImmunSymbArt,Immunité et Symbiose chez les Arthropodes(2010)
Subjects: 0106 biological sciences, Virulence, 010603 evolutionary biology, 01 natural sciences, Genome, 03 medical and health sciences, Symbiosis, Melanogaster, 030304 developmental biology, Genetics, 0303 health sciences, Experimental evolution, biology, Host (biology), [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Wolbachia, Drosophila, Drosophila melanogaster, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Coevolution, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: Evolutionary theory predicts that vertically transmitted symbionts are selected for low virulence, as their fitness is directly correlated to that of their host. In contrast with this prediction, theWolbachiastrainwMelPop drastically reduces itsDrosophila melanogasterhost lifespan at high rearing temperatures. It is generally assumed that this feature is maintained because theD. melanogaster–wMelPop symbiosis is usually not exposed to environmental conditions in which the symbiont is virulent. To test this hypothesis, we submittedwMelPop-infectedD. melanogasterlines to 17 generations of experimental evolution at a high temperature, while enforcing late reproduction by artificial selection. The fly survival was measured at different time points, as well as two traits that have been proposed to be causally responsible forwMelPop virulence: its relative density and the mean number of copies of octomom, an 8-genes region of theWolbachiagenome. We hypothesised that these conditions (high temperature and late reproduction) would select for a reducedwMelPop virulence, a reducedwMelPop density, and a reduced octomom copy number. Our results indicate that density, octomom copy number and virulence are correlated to each other. However, contrary to our expectations, we could not detect any reduction in virulence during the course of evolution. We discuss the significance of our results with respect to the evolutionary causes ofwMelPop virulence.
Published: 2020

22. Stress & Symbiosis: Heads or Tails?

Author: Fabrice Vavre, Alexis Bénard, Natacha Kremer, Génétique et évolution des interactions hôtes-parasites, Département génétique, interactions et évolution des génomes [LBBE] (GINSENG), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), JCJC grant RESIST (ANR-16- CE02-0013) LABEX ECOFECT (ANR-11-LABX-0048) of Université de Lyon, within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007), and ANR-16-CE02-0013,RESIST,Evolution rapide des interactions symbiotiques en réponse au stress : processus et mécanismes(2016)
Subjects: 0106 biological sciences, 0301 basic medicine, lcsh:Evolution, Context (language use), adaptation, Biology, 010603 evolutionary biology, 01 natural sciences, 03 medical and health sciences, Symbiosis, lcsh:QH540-549.5, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:QH359-425, stress-response mechanisms, Ecology, Evolution, Behavior and Systematics, Abiotic component, Ecology, Host (biology), biotic and abiotic stressors, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], 15. Life on land, beneficial symbiosis, symbiotic communities, Living systems, Holobiont, 030104 developmental biology, 13. Climate action, Evolutionary ecology, lcsh:Ecology, Adaptation, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: International audience; An increasing number of organisms are subjected to abiotic (e.g., air, water, and soil quality, temperature), but also biotic (e.g., new pathogens) stressors. These stressors may disturb the chemical and physiological homeostasis of living systems, and thus impact their ecology and evolution. Because eukaryotes are often associated with symbionts, these changes do not only impact the host but rather the holobiont, an assemblage of interacting species. Indeed, stressors can modify the symbiotic community composition and functions directly, but also indirectly through their impact on host physiology. Any disruption of the symbiotic homeostasis can then impact the host fitness. On the other side, several symbionts protect their host against various threats, and they may facilitate the adaptation of the holobiont to the new environment by limiting the negative impact of stress on the host. It now remains to clarify if their presence constitutes a driver of adaptation of the host or an obstacle limiting the selection of adaptive traits in the host, and to discuss if symbiosis is always the optimal strategy to cope with stressors. The reciprocal impact between stress and symbiosis can become more complex when stressors are considered in combination, as it occurs in nature. Indeed, synergistic or antagonistic effects may impact the holobiont response, and studies characterizing individual disturbances may not be sufficient. In the current context of climate change and globalized pollution, it is thus crucial to develop integrative approaches to predict how organisms, communities and ecosystems will face combinations of stressors.
Published: 2020
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23. An individual-based model to assess the spatial and individual heterogeneity of Brucella melitensis transmission in Alpine ibex

Author: Sophie Rossi, Pascal Marchand, Bruno Garin-Bastuji, Elodie Petit, Sébastien Lambert, Dominique Gauthier, Emmanuelle Gilot-Fromont, Carole Toïgo, Jean-Michel Gaillard, Anne Thébault, Systèmes de Référence Temps Espace (SYRTE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Biodémographie évolutive, Département écologie évolutive [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Office National de la Chasse et de la Faune Sauvage (ONCFS), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Direction de l'Evaluation des Risques (DER), This work was performed using the computing facilities of the CC LBBE/PRABI and of the CC IN2P3, and performed within the framework of the LABEX ECOFECT (ANR-11-LABX-0048) of Université de Lyon, within the program 'Investissements d'Avenir' (ANR- 11-IDEX-0007) operated by the French National Research Agency (ANR). The authors want to thank the scientific experts of the ANSES working groups on brucellosis of Alpine ibex in the Bargy massif, and especially Jean-Pierre Ganière and José-Maria Blasco, who helped for the range values of parameters for the sensitivity analysis. The authors also want to thank the field technicians and researchers, especially Jean Hars, from the French Wildlife and Hunting Agency (ONCFS), who performed monitoring and management of the Alpine ibex population. The authors are also grateful to Elizabeta Vergu and Benoit Durand for their precious insights with the design of the ABC calibration, to Vincent Miele for his help optimising the code of the model, to Christian Willisch for answering questions about Alpine ibex mating tactics and to Clément Calenge for his analyses of the social structure of Alpine ibex in our population. They also thank an anonymous referee for constructive comments on a previous version., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), and Direction de la Stratégie et des Programmes (DSP)
Subjects: 0106 biological sciences, education.field_of_study, Capra ibex, biology, Individual heterogeneity, 010604 marine biology & hydrobiology, Ecological Modeling, Population, biology.organism_classification, 010603 evolutionary biology, 01 natural sciences, 3. Good health, Spatial heterogeneity, law.invention, Individual based, Transmission (mechanics), law, Evolutionary biology, Spatial variability, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, education, ComputingMilieux_MISCELLANEOUS, Brucella melitensis
Abstract: Heterogeneity of infectious disease transmission can be generated by individual differences in the frequency of contacts with susceptible individuals, in the ability to transmit the infectious agent or in the duration of infection, and by spatial variation in the distribution, density or movements of hosts. Identifying spatial and individual heterogeneity can help improving management strategies to eradicate or mitigate infectious diseases, by targeting the individuals or areas that are responsible for most transmissions. Individual-based models allow quantifying the respective role of these sources of heterogeneity by integrating potential mechanisms that generate heterogeneity and then by tracking transmissions caused by each infected individual. In this study, we provide an individual-based model of endemic brucellosis Brucella melitensis transmission in the population of Alpine ibex (Capra ibex) of the Bargy massif (France) by taking advantage of detailed information available on ibex population dynamics, behaviour, and habitat use, and on epidemiological surveys. This host-pathogen system is expected to be subject of both individual and spatial heterogeneity. We first estimated the transmission probabilities, hitherto unknown, of the two main transmission routes of the infection (i.e., exposure to infectious births/abortions and venereal transmission). Then, we quantified heterogeneity at both individual and spatial levels. We found that both transmission routes are not negligible to explain the data, and that there is a high amount of heterogeneity of the host-pathogen system at the individual level, with females generating around 90% of the new cases of brucellosis infection. Males transmit infection at a lesser extent but still play a non-negligible role because they move between subpopulations and thereby create opportunities for spreading the infection spatially by venereal transmission. Two particular socio-spatial units are hotspots of transmission, and act as sources of transmission for the other units. These results may have important implications for disease management strategies.
Published: 2020

24. Persistent Legionnaires' Disease and Associated Antibiotic Treatment Engender a Highly Disturbed Pulmonary Microbiome Enriched in Opportunistic Microorganisms

Author: Christophe Rusniok, Christophe Ginevra, Ana Elena Pérez-Cobas, Sophie Jarraud, Carmen Buchrieser, Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Légionelles (CNR), This work was supported by the Institut Pasteur and the Agence National de Recherche (grant number ANR-15-CE17-0014-03 and grant number ANR-10-LABX-62IBEID to C.B. and A.E.P.-C.). Work in the S.J. laboratory is ﬁnanced by Santé Publique France and the Agence National de Recherche (grant number ANR-15-CE17-0014-01). C.G. and S.J. are part of the French Laboratory of Excellence project ECOFECT (grant number ANR-11-LABX-0048)., We thank the Institut Pasteur Biomics Pole (Christiane Bouchier and Laurence Ma) for sequencing of the samples reported in this study., ANR-15-CE17-0014,ProgLegio,Biomarqueurs bactériens et humains d'intérêt pronostic pour les légionelloses sévères(2015), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Lung microbiome, antibiotic resistance, Drug Resistance, Legionella Pneumonia, Opportunistic Infections, Microbiology, Legionella pneumophila, pulmonary microbiome, Host-Microbe Biology, 03 medical and health sciences, Antibiotic resistance, Virology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Pneumonia, Bacterial, medicine, Humans, pneumonia, Longitudinal Studies, Microbiome, Lung, Pathogen, Aged, 030304 developmental biology, 0303 health sciences, Bacteria, Whole Genome Sequencing, biology, 030306 microbiology, Microbiota, Fungi, Eukaryota, High-Throughput Nucleotide Sequencing, Genomics, biology.organism_classification, medicine.disease, QR1-502, Anti-Bacterial Agents, 3. Good health, respiratory tract diseases, Female, Legionnaires' disease, Legionnaires' Disease, Bronchoalveolar Lavage Fluid, Research Article
Abstract: The composition and dynamics of the lung microbiome during pneumonia are not known, although the lung microbiome might influence the severity and outcome of this infectious disease, similar to what was shown for the microbiome at other body sites. Here we report the findings of a comprehensive analysis of the lung microbiome composition of three patients with long-term pneumonia due to L. pneumophila and its evolution during antibiotic treatment. This work adds to our understanding of how the microbiome changes during disease and antibiotic treatment and points to microorganisms and their interactions that might be beneficial. In addition to bacteria and fungi, our analyses included archaea and eukaryotes (protozoa), showing that both are present in the pulmonary microbiota and that they might also play a role in the response to the microbiome disturbance., Despite the importance of pneumonia to public health, little is known about the composition of the lung microbiome during infectious diseases, such as pneumonia, and how it evolves during antibiotic therapy. To study the possible relation of the pulmonary microbiome to the severity and outcome of this respiratory disease, we analyzed the dynamics of the pathogen and the human lung microbiome during persistent infections caused by the bacterium Legionella pneumophila and their evolution during antimicrobial treatment. We collected 10 bronchoalveolar lavage fluid samples from three patients during long-term hospitalization due to pneumonia and performed a unique longitudinal study of the interkingdom microbiome, analyzing the samples for presence of bacteria, archaea, fungi, and protozoa by high-throughput Illumina sequencing of marker genes. The lung microbiome of the patients was characterized by a strong predominance of the pathogen, a low diversity of the bacterial fraction, and an increased presence of opportunistic microorganisms. The fungal fraction was more stable than the bacterial fraction. During long-term treatment, no genomic changes or antibiotic resistance-associated mutations that could explain the persistent infection occurred, according to whole-genome sequencing analyses of the pathogen. After antibiotic treatment, the microbiome did not recover rapidly but was mainly constituted of antibiotic-resistant species and enriched in bacteria, archaea, fungi, or protozoa associated with pathogenicity. The lung microbiome seems to contribute to nonresolving Legionella pneumonia, as it is strongly disturbed during infection and enriched in opportunistic and/or antibiotic-resistant bacteria and microorganisms, including fungi, archaea, and protozoa that are often associated with infections.
Published: 2020

25. Vaginal Tampon Colonization by Staphylococcus aureus in Healthy Women

Author: Dorian Bosquet, Alexia Barbry, Claire Prigent-Combaret, Myriam Chiaruzzi, Thibaut Durand, Anne Tristan, Sabine Bourdeau, Gerard Lina, Laurence Cluzeau, Anaëlle Muggeo, Cédric Badiou, Michèle Bes, Isaline Jacquemond, Astrid Engelmann, Daniel Muller, Jean Thioulouse, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecologie quantitative et évolutive des communautés, Département écologie évolutive [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), FINOVI foundation, ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), THIOULOUSE, Jean, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, and PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID
Subjects: medicine.disease_cause, Applied Microbiology and Biotechnology, healthy women, Menstruation, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Prevalence, 0303 health sciences, Ecology, Public and Environmental Health Microbiology, Middle Aged, Staphylococcal Infections, 3. Good health, medicine.anatomical_structure, vagina, Staphylococcus aureus, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Vagina, Female, France, menstruation, Biotechnology, Tampon, Adult, medicine.medical_specialty, Adolescent, Bacterial Toxins, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Intrauterine device, 03 medical and health sciences, Young Adult, medicine, Humans, Sex organ, Menstrual Hygiene Products, 030304 developmental biology, Gynecology, 030306 microbiology, business.industry, Toxic shock syndrome, Odds ratio, medicine.disease, equipment and supplies, colonization, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Food Science
Abstract: International audience; Tampons recovered from a cohort of 737 healthy women (median age, 32 years) were analyzed for the presence of Staphylococcus aureus. A total of 198 tampons (27%) were colonized by S. aureus, 28 (4%) by a strain producing toxic shock syndrome toxin 1 (TSST-1). S. aureus was detected more frequently in tampons that did not require an applicator for their insertion (74/233 [32%] versus 90/381 [24%]; odds ratio [OR] = 1.51 [95% confidence interval, 1.04 to 2.17]) and in women who used an intrauterine device for contraception (53/155 [34%] versus 145/572 [27%]; OR = 1.53 [95% confidence interval, 1.05 to 2.24]). The S. aureus strains isolated from tampons belonged to 22 different clonal complexes (CCs). The most prevalent CC was CC398 agr1 (n = 57 [27%]), a clone that does not produce superantigenic toxins, followed by CC30 agr3 (n = 27, 13%), producing TSST-1 (24/27 [89%]), the principal clone of S. aureus involved in menstrual toxic shock syndrome (MTSS).IMPORTANCE Menstrual toxic shock syndrome (MTSS) is an uncommon severe acute disease that occurs in healthy menstruating women colonized by TSST-1producing S. aureus who use intravaginal protection, such as tampons and menstrual cups. The catamenial product collected by the protection serves as a growth medium for S. aureus and allows TSST-1 production. Previous studies evaluated the prevalence of genital colonization by S. aureus by vaginal swabbing, but they did not examine tampon colonization. This study demonstrated a high prevalence of tampon colonization by S. aureus and the presence of the CC30 TSST-1 S. aureus clone responsible for MTSS in tampons from healthy women. The results support the vaginal carriage of this lineage in healthy women. In addition, the higher prevalence of S. aureus within tampons that do not require an applicator indicates a crucial role for handwashing before tampon handling to decrease the risk of tampon contamination.
Published: 2020

26. A behavior-manipulating virus relative as a source of adaptive genes for Drosophila parasitoids

Author: Benjamin Guinet, David Lepetit, Julien Varaldi, Bastien Bennetot, Yohann Couté, Olivier Bouchez, Deborah Di Giovanni, Matthieu Boulesteix, Marc Ravallec, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Ecologie Systématique et Evolution (ESE), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Eléments transposables, évolution, populations, Département génétique, interactions et évolution des génomes [LBBE] (GINSENG), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Etude de la dynamique des protéomes (EDyP ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Génome et Transcriptome - Plateforme Génomique ( GeT-PlaGe), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Diversité, Génomes & Interactions Microorganismes - Insectes [Montpellier] (DGIMI), Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique et évolution des interactions hôtes-parasites, ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-10-INBS-0006,HIDDEN,Extension de l'infrastructure de recherche dédiée aux maladies hautement infectieuses(2010), ANR-11-JSV7-0011,viromics,Distribution et impact des virus héritables dans une communauté hôtes-parasitoïdes(2011), Couté, Yohann, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, Extension de l'infrastructure de recherche dédiée aux maladies hautement infectieuses - - HIDDEN2010 - ANR-10-INBS-0006 - INBS - VALID, Jeunes Chercheuses et Jeunes Chercheurs - Distribution et impact des virus héritables dans une communauté hôtes-parasitoïdes - - viromics2011 - ANR-11-JSV7-0011 - JCJC - VALID, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), and Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0106 biological sciences, Gene Transfer, Horizontal, Genes, Viral, Genome, Insect, Wasps, Adaptation, Biological, Superparasitism, Hymenoptera, [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics, Leptopilina, 010603 evolutionary biology, 01 natural sciences, Parasitoid, Domestication, 03 medical and health sciences, Genetics, [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Animals, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Selection, Genetic, Clade, Symbiosis, Molecular Biology, Drosophila, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, Behavior, Animal, biology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Horizontal gene transfer, [SDV.EE.IEO] Life Sciences [q-bio]/Ecology, environment/Symbiosis, biology.organism_classification, Virus, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, Ichneumonoidea, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Evolutionary biology, Larva, [SDV.BA.ZI] Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, Female, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: Some species of parasitic wasps have domesticated viral machineries to deliver immunosuppressive factors to their hosts. Up to now, all described cases fall into the Ichneumonoidea superfamily, which only represents around 10% of hymenoptera diversity, raising the question of whether such domestication occurred outside this clade. Furthermore, the biology of the ancestral donor viruses is completely unknown. Since the 1980s, we know that Drosophila parasitoids belonging to the Leptopilina genus, which diverged from the Ichneumonoidea superfamily 225 Ma, do produce immunosuppressive virus-like structure in their reproductive apparatus. However, the viral origin of these structures has been the subject of debate. In this article, we provide genomic and experimental evidence that those structures do derive from an ancestral virus endogenization event. Interestingly, its close relatives induce a behavior manipulation in present-day wasps. Thus, we conclude that virus domestication is more prevalent than previously thought and that behavior manipulation may have been instrumental in the birth of such associations.
Published: 2020

27. Sequencing the Genome of Indian Flying Fox, Natural Reservoir of Nipah Virus, Using Hybrid Assembly and Conservative Secondary Scaffolding

Author: Julien Fouret, Frédéric G. Brunet, Martin Binet, Noémie Aurine, Francois Enchéry, Séverine Croze, Marie Guinier, Abdelghafar Goumaidi, Doris Preininger, Jean-Nicolas Volff, Marc Bailly-Bechet, Joël Lachuer, Branka Horvat, Catherine Legras-Lachuer, bViroscan3D, Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Inflammasome NLRP3 – NLRP3 Inflammasome, Immunobiologie des infections virales – Immunobiology of Viral Infections (IbIV), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Viroscan3D, Viroscan3D SAS [Lyon, France], Tiergarten Schönbrunn, Bioinformatique, phylogénie et génomique évolutive (BPGE), Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), ProfileXpert, Cancer Research Center of Lyon, INSERM, Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Direction Generale de l'Armement (DGA), ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), ROSSI, Sabine, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), and Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Microbiology (medical), lcsh:QR1-502, bats, Hybrid genome assembly, [SDV.GEN] Life Sciences [q-bio]/Genetics, Computational biology, Nipah virus, Microbiology, Genome, lcsh:Microbiology, Pteropus giganteus, 03 medical and health sciences, Natural reservoir, Original Research, 030304 developmental biology, Whole genome sequencing, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, biology, Contig, hybrid genome assembly, 030306 microbiology, biology.organism_classification, Pteropus, Pteropus medius, Medius, Nanopore sequencing, secondary scaffolding
Abstract: International audience; Indian fruit bats, flying fox Pteropus medius was identified as an asymptomatic natural host of recently emerged Nipah virus, which is known to induce a severe infectious disease in humans. The absence of P. medius genome sequence presents an important obstacle for further studies of virus–host interactions and better understanding of mechanisms of zoonotic viral emergence. Generation of the high-quality genome sequence is often linked to a considerable effort associated to elevated costs. Although secondary scaffolding methods have reduced sequencing expenses, they imply the development of new tools for the integration of different data sources to achieve more reliable sequencing results. We initially sequenced the P. medius genome using the combination of Illumina paired-end and Nanopore sequencing, with a depth of 57.4x and 6.1x, respectively. Then, we introduced the novel scaff2link software to integrate multiple sources of information for secondary scaffolding, allowing to remove the association with discordant information among two sources. Different quality metrics were next produced to validate the benefits from secondary scaffolding. The P. medius genome, assembled by this method, has a length of 1,985 Mb and consists of 33,613 contigs and 16,113 scaffolds with an NG50 of 19 Mb. At least 22.5% of the assembled sequences is covered by interspersed repeats already described in other species and 19,823 coding genes are annotated. Phylogenetic analysis demonstrated the clustering of P. medius genome with two other Pteropus bat species, P. alecto and P. vampyrus, for which genome sequences are currently available. SARS-CoV entry receptor ACE2 sequence of P. medius was 82.7% identical with ACE2 of Rhinolophus sinicus bats, thought to be the natural host of SARS-CoV. Altogether, our results confirm that a lower depth of sequencing is enough to obtain a valuable genome sequence, using secondary scaffolding approaches and demonstrate the benefits of the scaff2link application. The genome sequence is now available to the scientific community to (i) proceed with further genomic analysis of P. medius, (ii) to characterize the underlying mechanism allowing Nipah virus maintenance and perpetuation in its bat host, and (iii) to monitor their evolutionary pathways toward a better understanding of bats’ ability to control viral infections.
Published: 2020

28. Complex ecological interactions of Staphylococcus aureus in tampons during menstruation

Author: Michèle Bes, Gery Lamblin, Jean Thioulouse, Audrey Dubost, François Golfier, Isaline Jacquemond, Daniel Muller, Anne Tristan, Samuel Barreto, Yves Gillet, Danis Abrouk, Claude Alexandre Gustave, Tristan Ferry, Jean-Philippe Rasigade, Anaëlle Muggeo, Gerard Lina, Pierre Adrien Bolze, Claire Prigent-Combaret, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre National de Reference des Staphylocoques, Université de Lyon, Hôpital de la Croix-Rousse [CHU - HCL], Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Ecologie quantitative et évolutive des communautés, Département écologie évolutive [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie Gynécologique Oncologique et Obstétrique [CHU Lyon Sud], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], LABEX ECOFECT of Universite de Lyon within the programme 'Investissements d'Avenir' ANR-11-LABX-0048, ANR-11-IDEX-0007, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Davoine, Laure-Hélène, Service de Chirurgie Gynécologique et Oncologique – Obstétrique [CHU Lyon Sud], Service des Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse, CHU-HCL], Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)
Subjects: staphylococcus aureus, 0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], femme, 030106 microbiology, microbiome, Virulence, Severe disease, lcsh:Medicine, Biology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, medicine.disease_cause, Article, Microbiology, 03 medical and health sciences, microbiote, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Microbiome, lcsh:Science, ComputingMilieux_MISCELLANEOUS, cycle menstruel, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, communauté microbienne, Multidisciplinary, lcsh:R, Toxic shock syndrome, santé humaine, medicine.disease, During menstruation, equipment and supplies, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, medicine.anatomical_structure, Staphylococcus aureus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Vagina, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:Q, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Tampon
Abstract: Menstrual toxic shock syndrome (mTSS) is a severe disease that occurs in healthy women vaginally colonized by Staphylococcus aureus producing toxic shock toxin 1 and who use tampons. The aim of the present study was to determine the impact of the composition of vaginal microbial communities on tampon colonisation by S. aureus during menses. We analysed the microbiota in menstrual fluids extracted from tampons from 108 healthy women and 7 mTSS cases. Using culture, S. aureus was detected in menstrual fluids of 40% of healthy volunteers and 100% of mTSS patients. Between class analysis of culturomic and 16S rRNA gene metabarcoding data indicated that the composition of the tampons’ microbiota differs according to the presence or absence of S. aureus and identify discriminating genera. However, the bacterial communities of tampon fluid positive for S. aureus did not cluster together. No difference in tampon microbiome richness, diversity, and ecological distance was observed between tampon vaginal fluids with or without S. aureus, and between healthy donors carrying S. aureus and mTSS patients. Our results show that the vagina is a major niche of. S. aureus in tampon users and the composition of the tampon microbiota control its virulence though more complex interactions than simple inhibition by lactic acid-producing bacterial species.
Published: 2018

29. Overall Structural Model of NS5A Protein from Hepatitis C Virus and Modulation by Mutations Confering Resistance of Virus Replication to Cyclosporin A

Author: Stéphane Sarrazin, Véronique Receveur-Bréchot, Guy Lippens, Marie-Laure Fogeron, Ralf Bartenschlager, Roland Montserret, Sylvie Ricard-Blum, Volker Lohmann, Aurélie Badillo, Jennifer Molle, François-Xavier Cantrelle, Xavier Hanoulle, François Penin, Anja Böckmann, Frédéric Delolme, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Infectious Diseases [Heidelberg, Germany], Heidelberg University Hospital [Heidelberg], Agence Nationale de Recherches sur le Sida et les Hepatites Virales (ANRS) [A02007-2, A02011-2], French National Agency for Research [ANR-11-JSV8-005], [LABEX ECOFECT ANR-11-LABX-0048], French National Agency for Research (MAPPING Project) [ANR-11-BINF-0003], Deutsche Forschungsgemeinschaft [SFB/TRR83 TP13], CNRS (TGIR RMN THC) [FR-3050], Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)
Subjects: Models, Molecular, 0301 basic medicine, Protein Conformation, [SDV]Life Sciences [q-bio], Hepatitis C virus, Hepacivirus, Microbial Sensitivity Tests, Viral Nonstructural Proteins, Biology, Virus Replication, medicine.disease_cause, Antiviral Agents, Biochemistry, Mass Spectrometry, 03 medical and health sciences, Protein structure, Cyclosporin a, Drug Resistance, Viral, Genotype, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, NS5A, Mutation, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030104 developmental biology, Viral replication, Phosphoprotein, Cyclosporine
Abstract: International audience; Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a RNA-binding phosphoprotein composed of a N-terminal membrane anchor (AH), a structured domain 1 (D1), and two intrinsically disordered domains (D2 and D3). The knowledge of the functional architecture of this multifunctional protein remains limited. We report here that NS5A-D1D2D3 produced in a wheat germ cell-free system is obtained under a highly phosphorylated state. Its NMR analysis revealed that these phosphorylations do not change the disordered nature of D2 and D3 domains but increase the number of conformers due to partial phosphorylations. By combining NMR and small angle X-ray scattering, we performed a comparative structural characterization of unphosphorylated recombinant D2 domains of JFH1 (genotype 2a) and the Con1 (genotype 1b) strains produced in Escherichia coli. These analyses highlighted a higher intrinsic folding of the latter, revealing the variability of intrinsic conformations in HCV genotypes. We also investigated the effect of D2 mutations conferring resistance of HCV replication to cyclophilin A (CypA) inhibitors on the structure of the recombinant D2 Con1 mutants and their binding to CypA. Although resistance mutations D320E and R318W could induce some local and/or global folding perturbation, which could thus affect the kinetics of conformer interconversions, they do not significantly affect the kinetics of CypA/D2 interaction measured by surface plasmon resonance (SPR). The combination of all our data led us to build a model of the overall structure of NS5A, which provides a useful template for further investigations of the structural and functional features of this enigmatic protein.
Published: 2017

30. Vaccines inducing immunity to Lassa virus glycoprotein and nucleoprotein protect macaques after a single shot

Author: Audrey Vallve, Laura Barrot, Caroline Picard, Nicolas Baillet, Sylvain Baize, Hervé Raoul, Mathieu Mateo, Frédéric Tangy, Emeline Perthame, Alexandra Journeaux, Stéphanie Reynard, Natalia Pietrosemoli, Jean Armengaud, Lyne Fellmann, Xavier Carnec, Richard Allan, Caroline Carbonnelle, Stéphane Barron, Catherine Legras-Lachuer, Kenzo-Hugo Hillion, Jean-Charles Gaillard, Marie-Agnès Dillies, Justine Schaeffer, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), Viroscan3D SAS [Lyon, France], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Laboratoire P4 Jean Mérieux-Inserm [Lyon] (Unité de service 3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Européen de Recherche en Virologie et Immunologie [Lyon] (Tour Inserm CERVI), Université de Strasbourg (UNISTRA), Laboratoire Innovations technologiques pour la Détection et le Diagnostic (LI2D), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génomique virale et vaccination, This study was supported by the Grand Programme Fédérateur–Vaccinologie of the Institut Pasteur and the Fondation pour la Recherche Médicale (FRM team grant 2013). The MOPEVAC vaccine was supported by the LABEX ECOFECT (ANR-11-LABX-0048, Lyon University), within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007, French National Research Agency). The MeV-based LASV vaccines received funds from the Fondation pour l’Innovation en Infectiologie (FINOVI). M.M. was supported by a Pasteur Roux fellowship., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, Proteomics, 030106 microbiology, Biology, medicine.disease_cause, Measles, Cell Line, Measles virus, 03 medical and health sciences, Viral Proteins, Immune system, Lassa Fever, Immunity, medicine, Animals, Humans, Lassa fever, Lassa virus, Glycoproteins, Vaccination, General Medicine, medicine.disease, biology.organism_classification, Flow Cytometry, Virology, 3. Good health, Nucleoprotein, Macaca fascicularis, 030104 developmental biology, Nucleoproteins, Immunization, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Transcriptome
Abstract: International audience; Lassa fever is a major threat in Western Africa. The large number of people living at risk for this disease calls for the development of a vaccine against Lassa virus (LASV). We generated live-attenuated LASV vaccines based on measles virus and Mopeia virus platforms and expressing different LASV antigens, with the aim to develop a vaccine able to protect after a single shot. We compared the efficacy of these vaccines against LASV in cynomolgus monkeys. The vaccines were well tolerated and protected the animals from LASV infection and disease after a single immunization but with varying efficacy. Analysis of the immune responses showed that complete protection was associated with robust secondary T cell and antibody responses against LASV. Transcriptomic and proteomic analyses showed an early activation of innate immunity and T cell priming after immunization with the most effective vaccines, with changes detectable as early as 2 days after immunization. The most efficacious vaccine candidate, a measles vector simultaneously expressing LASV glycoprotein and nucleoprotein, has been selected for further clinical evaluation.
Published: 2019

31. A cohesin/HUSH- and LINC-dependent pathway controls ribosomal DNA double-strand break repair

Author: Vincent Rocher, Emiliano P. Ricci, Philippe E. Mangeot, Emmanuelle Guillou, Anne-Laure Finoux, Thomas Mangeat, Virginie Daburon, Coline Arnould, Gaëlle Legube, Aline Marnef, Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Contrôle traductionnel des ARNm eucaryotes et viraux – Translational control of Eukaryotic and Viral RNAs, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation Innovations en Infectiologie, ERC-StG-LS6-805500, European Research Council, Ligue Contre le Cancer, ANR-11-LABX-0048, Labex Ecofect, European Union's Horizon 2020, ANR-14-CE10-0002-01, Agence Nationale pour la Recherche, Institut National Contre le Cancer, ERC-2014-CoG 647344, European Research Council, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: DNA Repair, Nucleolus, Heterochromatin, Chromosomal Proteins, Non-Histone, Nuclear Envelope, LINC complex, cohesin, Cell Cycle Proteins, Biology, DNA, Ribosomal, DSB repair, LINC, Histones, 03 medical and health sciences, 0302 clinical medicine, Genetics, DNA Breaks, Double-Stranded, Homologous Recombination, Ribosomal DNA, 030304 developmental biology, HUSH, 0303 health sciences, ribosomal DNA, Cohesin, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Double Strand Break Repair, Chromatin, Cell biology, Gene Expression Regulation, 030220 oncology & carcinogenesis, chromatin, RNA, Long Noncoding, Homologous recombination, Cell Nucleolus, Developmental Biology, Research Paper
Abstract: International audience; The ribosomal DNA (rDNA) represents a particularly unstable locus undergoing frequent breakage. DNA double-strand breaks (DSBs) within rDNA induce both rDNA transcriptional repression and nucleolar segregation, but the link between the two events remains unclear. Here we found that DSBs induced on rDNA trigger transcriptional repression in a cohesin-and HUSH (human silencing hub) complex-dependent manner throughout the cell cycle. In S/G2 cells, transcriptional repression is further followed by extended resection within the interior of the nucleolus, DSB mobilization at the nucleolar periphery within nucleolar caps, and repair by homologous recombination. We showed that nuclear envelope invaginations frequently connect the nucleolus and that rDNA DSB mobilization, but not transcriptional repression, involves the nuclear envelope-associated LINC complex and the actin pathway. Altogether , our data indicate that rDNA break localization at the nucleolar periphery is not a direct consequence of transcriptional repression but rather is an active process that shares features with the mobilization of persistent DSB in active genes and heterochromatin.
Published: 2019

32. Subcutaneous suppressive antibiotic therapy for bone and joint infections: safety and outcome in a cohort of 10 patients

Author: Lippman, J., Braun, E., Servien, E., Batailler, C., Gaillard, R., Gunst, S., Roger, J., Fiquet, C., Viste, A., Chaudier, P., Besse, J. L., Louboutin, L., Gaudin, G., Ledru, T., Van Haecke, A., Ode, Q., Mercier, M., Alech-Tournier, F., Martres, S., Trouillet, F., Barrey, C., Jouanneau, E., Jacquesson, T., Gerenton, B., Mojallal, A., Boucher, F., Shipkov, H., Ceruse, P., Fuchsmann, C., Gleizal, A., Aubrun, F., Dziadzko, M., Macabeo, C., Beraut, L., Dupieux, C., Kolenda, C., JOSSE, J., Gustave, C. A., Craighero, F., Boussel, L., Pialat, J. B., Morelec, I., Tod, M., Gagnieu, M. C., Mabrut, E., Lyon Bone Joint Infection, Study, Goutelle, S., Lustig, S., Daoud, F., Fessy, M. H., Cohen, S., Laurent, F., Chidiac, C., Valour, F., Ferry, T., Perpoint, T., Miailhes, P., Ader, F., Becker, A., Roux, S., Triffault-Fillit, C., Conrad, A., Perry, M., Pouderoux, C., Service de Chirurgie Orthopédique [Centre Albert Trillat], Centre Albert Trillat [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Neuroimagerie cognitive (LCogn), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service hospitalo-universitaire de santé mentale et de thérapeutique, CHU Paris, Service de chirurgie maxillo-faciale et stomatologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hospices Civils de Lyon (HCL), RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Physiologie cardio-Respiratoire Expérimentale Théorique et Appliquée (TIMC-IMAG-PRETA), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Unite de Microbiologie Alimentaire et Previsionnelle, Ecole Nationale Vétérinaire de Lyon (ENVL), Centre National de Référence Legionella, Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales (MOTIVATE), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Physics [Ioannina), University of Ioannina, ARVALIS - Institut du végétal [Paris], Service des Maladies Infectieuses, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France, parent, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Equipe 15, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hosp Civils Lyon, Serv Malad Infect, Lyon, France, Institut für Physik [Rostock], Universität Rostock, Laboratoire de Mécanique et Technologie (LMT), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Centre interrégional de référence Rhône-Alpes - Auvergne des infections ostéo-articulaires complexes, University of Arizona, Agence Nationale de la Recherche, Hospices Civils de Lyon, ANR-11-LABX-0048, LABEX ECOFECT, ANR-11-IDEX-0007, Investissements d'Avenir, Institut des Sciences Chimiques de Rennes (ISCR), Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Rennes-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie cardio-Respiratoire Expérimentale Théorique et Appliquée (TIMC-PRETA), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Modeling & analysis for medical imaging and Diagnosis (MYRIAD)
Subjects: 0301 basic medicine, Microbiology (medical), Male, medicine.medical_specialty, medicine.medical_treatment, gram-negative bacilli, [SDV]Life Sciences [q-bio], 030106 microbiology, Salvage therapy, Arthritis, Prosthesis, Microbiology, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, ertapenem, medicine, Combined Modality Therapy, Humans, Pharmacology (medical), 030212 general & internal medicine, Pharmacology & Pharmacy, Prospective cohort study, risk-factors, carriage, Pharmacology, Arthritis, Infectious, business.industry, Drug Administration Routes, Osteomyelitis, medicine.disease, Prognosis, Magnetic Resonance Imaging, 3. Good health, Surgery, Anti-Bacterial Agents, Treatment Outcome, Infectious Diseases, chemistry, Ceftriaxone, Female, business, Tomography, X-Ray Computed, Ertapenem, pharmacokinetics, Cohort study, medicine.drug
Abstract: Background Optimal treatment of prosthetic joint infection and chronic osteomyelitis consists of surgical removal of biofilm-embedded bacteria, followed by a 6–12 week course of antimicrobial therapy. However, when optimal surgery is not feasible, oral prolonged suppressive antibiotic therapy (PSAT) is recommended to prevent prosthesis loosening and/or relapse of infection. Since 2010, we have used infection salvage therapy using off-label subcutaneous (sc) injection of a β-lactam as PSAT for patients in whom oral PSAT is not possible. Methods A single-centre prospective cohort study (2010–18) reporting treatment modalities, efficacy and safety in all patients receiving sc PSAT. NCT03403608. Results The 10 included patients (median age 79 years) had polymicrobial (n = 5) or MDR bacterial (n = 4) prosthetic joint infection (knee, n = 4; hip, n = 3) or chronic osteomyelitis (n = 3). After initial intensive therapy, seven patients received ertapenem, three patients received ceftriaxone and one patient received ceftazidime by sc injection (one patient received 8 days of ceftriaxone before receiving ertapenem). In one patient, sc PSAT failed with recurrent signs of infection under treatment. In three patients, sc PSAT had to be discontinued due to side effects; in only one of these was the sc route implicated (skin necrosis following direct sc injection and not gravity infusion). Median treatment duration was 433 days. In six patients, sc PSAT was successful with favourable outcome at the time of writing. Interestingly, three patients with MDR bacterial carriage at baseline lost this under PSAT during follow-up. Conclusions As salvage therapy, sc PSAT delivered by gravity infusion is a safe and interesting alternative when an optimal surgical strategy is not feasible and no oral treatment is available.
Published: 2019

33. The neutrophil to lymphocyte ratio indexes individual variation in the behavioural stress response of wild roe deer across fluctuating environmental conditions

Author: Jeanne Duhayer, Yannick Chaval, Joël Merlet, Maryline Pellerin, Jeffrey Carbillet, A. J. M. Hewison, François Débias, Typhaine Lavabre, Hélène Verheyden, Benjamin Rey, Sylvia Pardonnet, Jean-François Lemaître, Jean-Michel Gaillard, Emmanuelle Gilot-Fromont, Benoit Rannou, Corinne Régis, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Unité de recherche Comportement et Ecologie de la Faune Sauvage (CEFS), Institut National de la Recherche Agronomique (INRA), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Biodémographie évolutive, Département écologie évolutive [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Ecologie et évolution des populations, Observatoire du Mont-Blanc, Rongeurs Sauvages, Risques Sanitaires et Gestion des Populations - UR 1233 (RS2GP), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Office National de la Chasse et de la Faune Sauvage (ONCFS), INRA, VetAgro Sup and ONCFS, and was performed in the framework of the LABEX ECOFECT (ANR-11-LABX-0048) of Universite de Lyon, within the program 'Investissements d'Avenir' (ANR-11-IDEX-0007), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, [SDV]Life Sciences [q-bio], Population, Zoology, Biology, Stress, 010603 evolutionary biology, 01 natural sciences, Life history theory, Capreolus, biology.animal, N:L ratio, 0501 psychology and cognitive sciences, Behaviour, Environmental conditions, 050102 behavioral science & comparative psychology, Neutrophil to lymphocyte ratio, education, Ecology, Evolution, Behavior and Systematics, education.field_of_study, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, 05 social sciences, biology.organism_classification, Roe deer, Habitat, Animal ecology, Capreolus capreolus, Animal Science and Zoology, Conservation biology, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract: International audience; Understanding how wild animals adapt to perturbations and their consequences for life history traits and population dynamics is a current focus of attention in ecology and conservation biology. Here, we analysed variation in the neutrophil to lymphocyte ratio (N:L ratio), a proxy of stress level, in wild roe deer Capreolus capreolus from three populations experiencing markedly different environmental conditions. We first assessed whether among-individual differences in the N:L ratio were consistent over time and across environmental contexts. We then investigated how both individual characteristics (behaviour at capture, age, sex, body mass), and environmental context (habitat and year quality) were linked to this indicator of stress level. We found moderate, but consistent, repeatability of the N:L ratio in all three populations, indicating stable among-individual differences in the way individuals cope physiologically with varying environmental conditions. In addition, we found a weak, but consistent, association between the N:L ratio and behaviour at capture in two of the three populations. Finally, the N:L ratio also varied in relation to temporal changes in environmental conditions. In particular, individuals had, on average, higher levels of stress in poor-quality years in two of the three populations. We discuss our results in relation to the coping styles framework. Significance statement Due to global change, natural populations are increasingly faced with unpredictable fluctuations of their environment. The stress response, via the release of glucocorticoids, is a key mechanism that enables individuals to cope with these variations. However, all individuals do not necessarily cope with life threatening and/or stressful situations in the same way, but as yet, the major drivers underlying variation in stress level remain unclear. We showed that the N:L ratio, reflecting baseline stress level, was repeatable and influenced by both individual and environmental factors. In particular, variation in the N:L ratio was linked to the quality of the year in terms of resource availability and, to a lesser extent, to the individual's behaviour at capture. Our study demonstrates that both environmental context and individual characteristics drive variation in the N:L ratio in a wild vertebrate population.
Published: 2019

34. Does body growth impair immune function in a large herbivore?

Author: Jean-François Lemaître, Hélène Verheyden, Jeffrey Carbillet, François Débias, Maryline Pellerin, Sylvia Pardonnet, Frédéric Douhard, Jean-Michel Gaillard, Emmanuelle Gilot-Fromont, Benjamin Rey, Aiden J Mark Hewison, Louise Cheynel, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biodémographie évolutive, Département écologie évolutive [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Unité de recherche Comportement et Ecologie de la Faune Sauvage (CEFS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Office National de la Chasse et de la Faune Sauvage (ONCFS), ONCFS : 2011/18/6171 et ONCFS : 2015/19/6171, ANR-15-CE32-0002,AGEX,Vieillissement sexe-spécifique en milieu naturel(2015), ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), Ecotoxicologie & Santé des écosystèmes - ECSECO (ECI), Institut National de la Recherche Agronomique (INRA)-Laboratoire Ecologie Fonctionnelle et Environnement (ECOLAB), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Recherche Agronomique (INRA), Département d'Astrophysique, de physique des Particules, de physique Nucléaire et de l'Instrumentation Associée (DAPNIA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Ecologie Fonctionnelle et Environnement (ECOLAB), Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut Ecologie et Environnement (INEE), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Agence Nationale de la Recherche ANR-15-CE32-0002-01 / ONCFS 2011/18/6171 2015/19/6171 / LABEX ECOFECT of Universite de Lyon within the program 'Investissementsd'Avenir' ANR-11-LABX-0048 ANR-11-IDEX-0007, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-École nationale supérieure agronomique de Toulouse (ENSAT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP)
Subjects: Adult, 0106 biological sciences, animal diseases, Population, Zoology, Trade-off, Biology, 010603 evolutionary biology, 01 natural sciences, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Capreolus, Immune system, Immunity, biology.animal, Animals, Herbivory, education, Life history, Ecology, Evolution, Behavior and Systematics, ComputingMilieux_MISCELLANEOUS, Roe deer, Herbivore, education.field_of_study, Reproductive success, Deer, Reproduction, 010604 marine biology & hydrobiology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Phenotype, Body mass, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, bacteria, Female, Eco-immunology, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract: International audience; According to the principle of allocation, trade-offs are inevitable when resources allocated to one biological function are no longer available for other functions. Growth, and to a lesser extent, immunity are energetically costly functions that may compete with allocation to reproductive success and survival. However, whether high allocation to growth impairs immune system development during the growing period or immune system performance during adulthood is currently unknown in wild mammals. Using three roe deer (Capreolus capreolus) populations experiencing contrasting environmental conditions, we tested for potential costs of growth on immune phenotype over both the short-term (during growth), and the long-term (during adulthood) over the course of an individuals' life. We investigated potential costs on a set of 12 immune traits that reflect both innate and adaptive responses, and compared them between sexes and populations. Although fast growth tended to be associated with low levels of some humoral traits (globulins) during the growing period and some cellular immune traits (i.e. eosinophil and neutrophil counts) during adulthood, evidence for a trade-off between growth and other immune components was limited. Unexpectedly, no detectable growth costs on immunity were found in females from the population experiencing the least favourable environment. We discuss our findings in the light of the complex interplay between resource allocation strategies among reproduction, maintenance and immunity, in relation to local environmental conditions experienced by roe deer.
Published: 2019

35. Coexistence of two sympatric cryptic bat species in French Guiana: insights from genetic, acoustic and ecological data

Author: Corinne Régis, Guillaume Queney, Dominique Pontier, Jean-Baptiste Pons, Lina Muselet, Cécile Kaerle, Elodie Portanier, Eric J. Petit, Damien M. de Vienne, Ondine Filippi-Codaccioni, David Fouchet, Marie-Pauline Beugin, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Ecoépidémiologie évolutionniste, Département écologie évolutive [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Bioinformatique, phylogénie et génomique évolutive (BPGE), Département PEGASE [LBBE] (PEGASE), Ecologie et évolution des populations, Antagene - Animal Genomics Laboratory, Écologie et santé des écosystèmes (ESE), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Université de Lyon, ANR-11-LABX-0048, and ANR-11-IDEX-0007
Subjects: 0106 biological sciences, 0301 basic medicine, Population genetics, 01 natural sciences, Haplogroup, Chiroptera, Phylogeny, education.field_of_study, biology, Reproduction, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Reproductive isolation, Mitochondrial DNA, French Guiana, Pteronotus cf, Sympatry, Genetic structure, Pteronotus cf. parnellii, Research Article, Species complex, Neotropics, Genotype, Evolution, Population, Introgression, 010603 evolutionary biology, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Species Specificity, Pteronotus, [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, QH359-425, otorhinolaryngologic diseases, Animals, parnellii, Microsatellite, Echolocation, Asymmetric introgression, education, Ecosystem, Ecology, Evolution, Behavior and Systematics, Cell Nucleus, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Acoustics, biology.organism_classification, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, 030104 developmental biology, Evolutionary biology, Microsatellite Repeats, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: Background The distinction between lineages of neotropical bats from the Pteronotus parnellii species complex has been previously made according to mitochondrial DNA, and especially morphology and acoustics, in order to separate them into two species. In these studies, either sample sizes were too low when genetic and acoustic or morphological data were gathered on the same individuals, or genetic and other data were collected on different individuals. In this study, we intensively sampled bats in 4 caves and combined all approaches in order to analyse genetic, morphologic, and acoustic divergence between these lineages that live in the same caves in French Guiana. Results A multiplex of 20 polymorphic microsatellite markers was developed using the 454-pyrosequencing technique to investigate for the first time the extent of reproductive isolation between the two lineages and the population genetic structure within lineages. We genotyped 748 individuals sampled between 2010 and 2015 at the 20 nuclear microsatellite loci and sequenced a portion of the cytochrome c oxydase I gene in a subset of these. Two distinct, non-overlapping haplogroups corresponding to cryptic species P. alitonus and P. rubiginosus were revealed, in accordance with previous findings. No spatial genetic structure between caves was detected for both species. Hybridization appeared to be quite limited (0.1–4%) using microsatellite markers whereas introgression was more common (7.5%) and asymmetric for mitochondrial DNA (mtDNA). Conclusions The extremely low rate of hybridization could be explained by differences in life cycle phenology between species as well as morphological and acoustical distinction between sexes in one or the other species. Taken together, these results add to our growing understanding of the nature of species boundaries in Pteronotus parnelli, but deserve more in-depth studies to understand the evolutionary processes underlying asymmetric mtDNA introgression in this group of cryptic species. Electronic supplementary material The online version of this article (10.1186/s12862-018-1289-8) contains supplementary material, which is available to authorized users.
Published: 2018

36. A Vaccine Platform against Arenaviruses Based on a Recombinant Hyperattenuated Mopeia Virus Expressing Heterologous Glycoproteins

Author: Stéphane Barron, Sylvain Baize, Elsie Laban Yekwa, Hervé Raoul, Audrey Page, Stéphanie Reynard, Mathieu Mateo, Xavier Carnec, Audrey Vallve, Laura Barrot, Jimmy Hortion, Caroline Picard, François Ferron, Caroline Carbonnelle, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Architecture et fonction des macromolécules biologiques (AFMB), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Laboratoire P4 Jean Mérieux-Inserm [Lyon] (Unité de service 3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Européen de Recherche en Virologie et Immunologie [Lyon] (Tour Inserm CERVI), This work was supported by the Fondation pour l'Innovation en Infectiologie (FINOVI) (Lyon, France), the Fondation pour la Recherche Médicale (FRM) (France), French National Research Agency grant ANR-11-BSV_019-02, and the Fondation Méditerranée Infection. This work was also supported by Labex Ecofect (grant ANR-11-LABX-0048, Lyon University) within the program Investissements d'Avenir (grant ANR-11-IDEX-0007, French National Research Agency)., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], ANR-11-IDEX-0007-02/11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), and ANR-11-IDEX-0007-02/11-IDEX-0007,Avenir L.S.E.,Avenir L.S.E.(2011)
Subjects: 0301 basic medicine, viruses, MESH: Monkey Diseases/prevention & control, viral hemorrhagic fevers, MESH: Cricetinae, medicine.disease_cause, MESH: Lassa Fever/prevention & control, MESH: Lassa Fever/virology, Cricetinae, Chlorocebus aethiops, MESH: Animals, Arenaviridae, Lassa fever, arenavirus, innate immunity, MESH: Arenaviridae/genetics, biology, MESH: Arenaviridae/immunology, Viral Vaccine, Monkey Diseases, Vaccination, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 3. Good health, Hemorrhagic Fevers, MESH: Monkey Diseases/virology, MESH: HEK293 Cells, Interferon Type I, MESH: Lassa virus/immunology, MESH: Hemorrhagic Fevers, Viral/transmission, MESH: Lassa Fever/immunology, MESH: Interferon Type I/immunology, MESH: Viral Vaccines/immunology, Hemorrhagic Fevers, Viral, live-vector vaccines, Immunology, MESH: Vero Cells, MESH: Hemorrhagic Fevers, Viral/pathology, Vaccines, Attenuated, Microbiology, Virus, Cell Line, 03 medical and health sciences, Virology, Vaccines and Antiviral Agents, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Lassa virus, Vero Cells, Arenavirus, MESH: Humans, MESH: Vaccines, Attenuated/immunology, Viral Vaccines, MESH: Monkey Diseases/immunology, MESH: Vaccination, biology.organism_classification, medicine.disease, MESH: Cercopithecus aethiops, MESH: Hemorrhagic Fevers, Viral/immunology, MESH: Exoribonucleases/metabolism, MESH: Cell Line, Macaca fascicularis, HEK293 Cells, 030104 developmental biology, MESH: Macaca fascicularis, MESH: Hemorrhagic Fevers, Viral/virology, Insect Science, Junin virus, Exoribonucleases
Abstract: Several Old World and New World arenaviruses are responsible for severe endemic and epidemic hemorrhagic fevers, whereas other members of the Arenaviridae family are nonpathogenic. To date, no approved vaccines, antivirals, or specific treatments are available, except for Junín virus. However, protection of nonhuman primates against Lassa fever virus (LASV) is possible through the inoculation of the closely related but nonpathogenic Mopeia virus (MOPV) before challenge with LASV. We reasoned that this virus, modified by using reverse genetics, would represent the basis for the generation of a vaccine platform against LASV and other pathogenic arenaviruses. After showing evidence of exoribonuclease (ExoN) activity in NP of MOPV, we found that this activity was essential for multiplication in antigen-presenting cells. The introduction of multiple mutations in the ExoN site of MOPV NP generated a hyperattenuated strain (MOPV ExoN6b ) that is (i) genetically stable over passages, (ii) has increased immunogenic properties compared to those of MOPV, and (iii) still promotes a strong type I interferon (IFN) response. MOPV ExoN6b was further modified to harbor the envelope glycoproteins of heterologous pathogenic arenaviruses, such as LASV or Lujo, Machupo, Guanarito, Chapare, or Sabia virus in order to broaden specific antigenicity while preserving the hyperattenuated characteristics of the parental strain. Our MOPV-based vaccine candidate for LASV, MOPEVAC LASV , was used in a one-shot immunization assay in nonhuman primates and fully protected them from a lethal challenge with LASV. Thus, our hyperattenuated strain of MOPV constitutes a promising new live-attenuated vaccine platform to immunize against several, if not all, pathogenic arenaviruses. IMPORTANCE Arenaviruses are emerging pathogens transmitted to humans by rodents and responsible for endemic and epidemic hemorrhagic fevers of global concern. Nonspecific symptoms associated with the onset of infection make these viruses difficult to distinguish from other endemic pathogens. Moreover, the unavailability of rapid diagnosis in the field delays the identification of the virus and early care for treatment and favors spreading. The vaccination of exposed populations would be of great help to decrease morbidity and human-to-human transmission. Using reverse genetics, we generated a vaccine platform for pathogenic arenaviruses based on a modified and hyperattenuated strain of the nonpathogenic Mopeia virus and showed that the Lassa virus candidate fully protected nonhuman primates from a lethal challenge. These results showed that a rationally designed recombinant MOPV-based vaccine is safe, immunogenic, and efficacious in nonhuman primates.
Published: 2018

37. Tick-Bacteria Mutualism Depends on B Vitamin Synthesis Pathways

Author: Renaud Lancelot, Marie Buysse, Etienne Loire, Olivier Bouchez, Fabrice Vavre, Florian Binetruy, Laurence Vial, Olivier Duron, Valérie Noël, Claudine Menard, Olivier Morel, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Evolution of host-microbe communities (MIVEGEC-EVCO), Processus Écologiques et Évolutifs au sein des Communautés (PEEC), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Génétique et évolution des interactions hôtes-parasites, Département génétique, interactions et évolution des génomes [LBBE] (GINSENG), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Evolution Théorique et Expérimentale (MIVEGEC-ETE), Perturbations, Evolution, Virulence (PEV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA), Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Génétique Cellulaire (LGC), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), CNRS, IRD, CIRAD, Laboratoire d'Excellence CEBA, France Genomique National infrastructure as part of the 'Investissement d'Avenir' program [ANR-10-INBS-09], French Ministry for National Education and Research, VetAgroSup, LABEX ECOFECT of Universite de Lyon, within the program 'Investissements d'Avenir' [ANR-11-LABX-0048, ANR-11-IDEX-0007], Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Vétérinaire de Toulouse (ENVT), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, Male, 030106 microbiology, Tick, L73 - Maladies des animaux, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Ornithodoros moubata, Animals, L50 - Physiologie et biochimie animales, Francisella, Rickettsia, Ornithodoros, Symbiosis, Gene, ComputingMilieux_MISCELLANEOUS, Mutualism (biology), Genetics, biology, Obligate, Intracellular parasite, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], 000 - Autres thèmes, L10 - Génétique et amélioration des animaux, biology.organism_classification, bacterial infections and mycoses, Biosynthetic Pathways, B vitamins, 030104 developmental biology, Vitamin B Complex, bacteria, Female, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, General Agricultural and Biological Sciences, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: Summary Mutualistic interactions with microbes have facilitated the radiation of major eukaryotic lineages [ 1 , 2 ]. Microbes can notably provide biochemical abilities, allowing eukaryotes to adapt to novel habitats or to specialize on particular feeding niches [ 2 , 3 , 4 ]. To investigate the importance of mutualisms for the exclusive blood feeding habits of ticks, we focused on a bacterial genus of medical interest, Francisella, which is known to include both virulent intracellular pathogens of vertebrates [ 5 , 6 ] and maternally inherited symbionts of ticks [ 7 , 8 , 9 ]. Through a series of physiological experiments, we identified a Francisella type, F-Om, as an obligate nutritional mutualist in the life cycle of the African soft tick Ornithodoros moubata. Francisella F-Om mutualism synthesizes B vitamins that are deficient in the blood meal of ticks. Indeed, experimental elimination of Francisella F-Om resulted in alteration of tick life history traits and physical abnormalities, deficiencies which were fully restored with an oral supplement of B vitamins. We also show that Francisella F-Om is maternally transmitted to all maturing tick oocytes, suggesting that this heritable symbiont is an essential adaptive element in the life cycle of O. moubata. The Francisella F-Om genome further revealed a recent origin from a Francisella pathogenic life style, as observed in other Francisella symbionts [ 6 , 7 , 10 ]. Though half of its protein-coding sequences are now pseudogenized or lost, Francisella F-Om has kept several B vitamin synthesis pathways intact, confirming the importance of these genes in evolution of its nutritional mutualism with ticks.
Published: 2018

38. Impact of currently marketed tampons and menstrual cups on Staphylococcus aureus growth and TSST-1 production in vitro

Author: Nonfoux, Louis, Chiaruzzi, Myriam, Badiou, Cédric, Baude, Jessica, Tristan, Anne, Thioulouse, Jean, Muller, Daniel, Prigent Combaret, Claire, Lina, Gérard, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Labex Ecofect of the Universite de Lyon within the program Investissements d'Avenir ANR-11-LABX-0048 ANR-11IDEX-0007, FINOVI Foundation, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: menstrual cup, Staphylococcus aureus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, toxic shock syndrome toxin 1, [SDV.IMM]Life Sciences [q-bio]/Immunology, tampon, equipment and supplies, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, biofilm, elastomer, fiber
Abstract: International audience; Fifteen currently marketed intravaginal protection products (11 types of tampon and four menstrual cups) were tested by the modified tampon sac method to determine their effect on Staphylococcus aureus growth and toxic shock toxin 1 (TSST-1) production. Most tampons reduced S. aureus growth and TSST-1 production, with differences based on brand and composition, and S. aureus growth was higher in de-structured than in unaltered tampons. We observed higher S. aureus growth and toxin production in menstrual cups than in tampons, potentially due to the additional air introduced to the bag by cups, with differences based on cup composition and size.Importance Menstrual toxic shock syndrome is a rare but severe disease. It occurs in healthy women vaginally colonized by Staphylococcus aureus producing toxic shock syndrome toxin 1 using intravaginal protection such as tampons or menstrual cups. Intravaginal protection induces TSS production by collecting catamenial products which act as a growth medium for S. aureus Previous studies have evaluated the impact of tampon composition on S. aureus producing toxic shock syndrome toxin 1, but they are not recent and did not include menstrual cups. This study demonstrates that highly reproducible results for S. aureus growth and TSST-1 production can be obtained using a simple protocol that reproduces the physiological conditions of tampon and cup usage as closely as possible, providing recommendations for tampon or cup use to both manufacturers and consumers. Notably, our results do not show that menstrual cups are safer than tampons and suggest that they require similar precautions.
Published: 2018

39. How to Control HTLV-1-Associated Diseases: Preventing de Novo Cellular Infection Using Antiviral Therapy

Author: Amandine Pasquier, Sandrine Alais, Loic Roux, Maria-Isabel Thoulouze, Karine Alvarez, Chloé Journo, Hélène Dutartre, Renaud Mahieux, Davoine, Laure-Hélène, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Oncogenèse rétrovirale – Retroviral Oncogenesis (OR), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Architecture et fonction des macromolécules biologiques (AFMB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), La Ligue Contre le Cancer (Equipe Labellisee Mahieux) EL2013-3, ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), Oncogenèse rétrovirale – Retroviral Oncogenesis, Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Virologie Structurale, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: 0301 basic medicine, Microbiology (medical), [SDV.IMM] Life Sciences [q-bio]/Immunology, viruses, proviral load, lcsh:QR1-502, Microbiology, lcsh:Microbiology, 03 medical and health sciences, Zidovudine, cell\textendashcell transmission, In vivo, immune system diseases, prodrugs, hemic and lymphatic diseases, Tropical spastic paraparesis, antiviral therapy, Adefovir, Medicine, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, business.industry, virus diseases, medicine.disease, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Reverse transcriptase, acyclic nucleoside phosphonates and thiophosphonates, 3. Good health, Leukemia, 030104 developmental biology, Viral replication, HTLV-1, AZT, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, CD8, medicine.drug
Abstract: International audience; Five to ten million individuals are infected by Human T-cell Leukemia Virus type 1 (HTLV-1). HTLV-1 is transmitted through prolonged breast-feeding, by sexual contacts and by transmission of infected T lymphocytes through blood transfusion. One to ten percent of infected carriers will develop a severe HTLV-1-associated disease: Adult-T-cell leukemia/lymphoma (ATLL), or a neurological disorder named Tropical Spastic Paraparesis/HTLV-1 Associated Myelopathy (TSP/HAM). In vivo, HTLV-1 is mostly detected in CD4+ T-cells, and to a lesser extent in CD8+ T cells and dendritic cells. There is a strong correlation between HTLV-1 proviral load (PVL) and clinical status of infected individuals. Thus, reducing PVL could be part of a strategy to prevent or treat HTLV-1-associated diseases among carriers. Treatment of ATLL patients using conventional chemotherapy has very limited benefit. Some chronic and acute ATLL patients are, however, efficiently treated with a combination of interferon α and zidovudine (IFN-α/AZT), to which arsenic trioxide is added in some cases. On the other hand, no efficient treatment for TSP/HAM patients has been described yet. It is therefore crucial to develop therapies that could either prevent the occurrence of HTLV-1-associated diseases or at least block the evolution of the disease in the early stages. In vivo, reverse transcriptase (RT) activity is low in infected cells, which is correlated with a clonal mode of viral replication. This renders infected cells resistant to nucleoside RT inhibitors such as AZT. However, histone deacetylase inhibitors (HDACi) associated to AZT efficiently induces viral expression and prevent de novo cellular infection. In asymptomatic STLV-1 infected non-human primates, HDACi/AZT combination allows a strong decrease in the PVL. Unfortunately, rebound in the PVL occurs when the treatment is stopped, highlighting the need for better antiviral compounds. Here, we review previously used strategies targeting HTLV-1 replication. We also tested a series of HIV-1 RT inhibitors in an in vitro anti-HTLV-1 screen, and report that bis-POM-PMEA (adefovir dipivoxil) and bis-POC-PMPA (tenofovir disoproxil) are much more efficient compared to AZT to decrease HTLV-1 cell-to-cell transmission in vitro. Our results suggest that revisiting already established antiviral drugs is an interesting approach to discover new anti-HTLV-1 drugs.
Published: 2018

40. Virology and cell biology of the hepatitis C virus life cycle – An update

Author: Jean Dubuisson, François-Loïc Cosset, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), LabEx ECOFECT Inserm U1111, Work in the JD laboratory was supported by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) and ANR through ERA-NET Infect-ERA program (ANR-13-IFEC-0002-01). Work in the FLC laboratory was supported by ANRS, the European Research Council (ERC-2008-AdG-233130-HEPCENT) and the LabEx ECOFECT (ANR-11-LABX-0048) of Université de Lyon., We thank Laurence Cocquerel and Marlène Dreux for critical reading of the manuscript and Sophana Ung for help with the Figures. We apologize to all colleagues whose work could not be referenced because of length restriction., Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cirrhosis, MESH: Virus Replication/physiology, [SDV]Life Sciences [q-bio], Hepacivirus, medicine.disease_cause, Virus Replication, MESH: Hepacivirus/growth & development, Virus entry, MESH: RNA, Viral/physiology, MESH: Hepatitis C/pathology, MESH: Cell Biology/trends, education.field_of_study, MESH: Life Cycle Stages/physiology, Hepatitis C virus, Viral life cycle, MESH: Hepacivirus/pathogenicity, virus diseases, MESH: Hepatitis C/physiopathology, Hepatitis C, 3. Good health, Interaction with host, Hepatocellular carcinoma, MESH: Hepacivirus/genetics, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, MESH: Virology/trends, Population, Biology, Virus-host interactions, MESH: Lipid Metabolism/physiology, Virology, medicine, Humans, education, Hepatitis, Life Cycle Stages, MESH: Humans, Hepatology, Cell Biology, medicine.disease, Lipid Metabolism, digestive system diseases, MESH: Hepatocytes/pathology, MESH: Hepatocytes/virology, Immunology, Hepatocytes, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Affiliations ECOFECT; International audience; Hepatitis C virus (HCV) is an important human pathogen that causes hepatitis, liver cirrhosis and hepatocellular carcinoma. It imposes a serious problem to public health in the world as the population of chronically infected HCV patients who are at risk of progressive liver disease is projected to increase significantly in the next decades. However, the arrival of new antiviral molecules is progressively changing the landscape of hepatitis C treatment. The search for new anti-HCV therapies has also been a driving force to better understand how HCV interacts with its host, and major progresses have been made on the various steps of the HCV life cycle. Here, we review the most recent advances in the fast growing knowledge on HCV life cycle and interaction with host factors and pathways.
Published: 2014
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41. Daclatasvir Prevents Hepatitis C Virus Infectivity by Blocking Transfer of Viral Genome to Assembly Sites

Author: Christophe Chamot, Solène Denolly, François-Loïc Cosset, Fanny Turlure, Marlène Dreux, Bertrand Boson, Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), SFR Biosciences, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), European Project: 233130,EC:FP7:ERC,ERC-2008-AdG,HEPCENT(2009), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Boson, Bertrand, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, Molecular Analysis of Hepatitis C Virus Neutralization and Entry For the Development of Novel Antiviral Immunopreventive Strategies - HEPCENT - - EC:FP7:ERC2009-04-01 - 2014-03-31 - 233130 - VALID, and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: 0301 basic medicine, Daclatasvir, Pyrrolidines, Hepatitis C virus, viruses, 030106 microbiology, Mutant, Genome, Viral, Hepacivirus, Biology, Viral Nonstructural Proteins, medicine.disease_cause, Antiviral Agents, RNA Transport, 03 medical and health sciences, Multiplicity of infection, Viral Envelope Proteins, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cell Line, Tumor, medicine, Humans, chronic hepatitis C, NS5A, DAA, Infectivity, direct-acting antiviral agent, Hepatology, Endoplasmic reticulum, Viral Core Proteins, Virus Assembly, Gastroenterology, Imidazoles, virus diseases, Valine, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Virology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, 3. Good health, Protein Transport, 030104 developmental biology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, RNA, Viral, Carbamates, Biogenesis, medicine.drug
Abstract: Daclatasvir is a direct-acting antiviral agent and potent inhibitor of NS5A, which is involved in replication of the hepatitis C virus (HCV) genome, presumably via membranous web shaping, and assembly of new virions, likely via transfer of the HCV RNA genome to viral particle assembly sites. Daclatasvir inhibits the formation of new membranous web structures and, ultimately, of replication complex vesicles, but also inhibits an early assembly step. We investigated the relationship between daclatasvir-induced clustering of HCV proteins, intracellular localization of viral RNAs and inhibition of viral particle assembly., HCVcc particles were produced from Huh7.5 hepatocarcinoma cells in presence of daclatasvir for short time periods. Infectivity as well as production of physical particles were quantified and producer cells were subjected to subcellular fractionation. Intracellular colocalization between core, E2, NS5A, NS4B proteins, and viral RNAs was quantitatively analyzed by confocal microscopy and by structured illumination microscopy., Short exposure of HCV-infected cells to daclatasvir reduced viral assembly and induced clustering of structural proteins with non-structural HCV proteins, including core, E2, NS4B and NS5A. These clustered structures appeared to be inactive assembly platforms, likely owing to loss of functional connection with replication complexes. Daclatasvir greatly reduced delivery of viral genomes to these core clusters without altering HCV RNA colocalization with NS5A. In contrast, daclatasvir neither induced clustered structures nor inhibited HCV assembly in cells infected with a daclatasvir-resistant mutant (NS5A-Y93H), indicating that daclatasvir targets a mutual, specific function of NS5A inhibiting both processes., In addition to inhibiting replication complex biogenesis, daclatasvir prevents viral assembly by blocking transfer of the viral genome to assembly sites. This leads to clustering of HCV proteins, because viral particles and replication complex vesicles cannot form and/or egress. This dual mode of action of daclatasvir could explain its efficacy in blocking HCV replication in cultured cells and in treatment of patients with HCV infection.
Published: 2016

42. Bioecological Drivers of Rabies Virus Circulation in a Neotropical Bat Community

Author: Benoit de Thoisy, Anne Lavergne, Dominique Pontier, Rachel Lavenir, Damien Donato, Hervé Bourhy, Laurent Dacheux, Arielle Salmier, Vincent Lacoste, Marguerite Delaval, Edith Darcissac, Amandine Guidez, Florence Larrous, Laboratoire des Interactions Virus-Hôtes [Cayenne, Guyane Française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de Référence de la Rage-Dynamique des Lyssavirus et adaptation à l'hôte (CNR), Institut Pasteur [Paris] (IP), Service développement Sylvétude [Réserve Montabo, Cayenne], ONF - Direction régionale de la Guyane [Cayenne], Office national des forêts (ONF)-Office national des forêts (ONF), Ecoépidémiologie évolutionniste, Département écologie évolutive [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), This study was conducted within the ViRUSES and CAROLIA programs supported by European funds (ERDF/FEDER) and assistance from Région Guyane and Direction Régionale pour la Recherche et la Technologie. It also received a European commission REGPOT-CT-2011-285837-STRonGer' grant within the FP7 and 'Investissement d’ Avenir' Grants managed by Agence Nationale de la Recherche (CEBA, Ref. ANR-10- LABX-25-01 ECOFECT, Ref. ANR-11-LABX-0048). The authors thank the Institut de Veille Sanitaire, Saint-Maurice, France (http://www.invs.sante.fr/) and the Institut Pasteur for their financial contribution to the NationalReference Centre for Rabies that made this work possible. This research was also funded by the European Union Seventh framework Programme (FP7/2007-2013) PREDEMICS grant 278433., ANR-10-LABX-0025,CEBA,CEnter of the study of Biodiversity in Amazonia(2010), ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), European Project: ERDF/FEDER,ViRUSES, European Project: 285837,EC:FP7:REGPOT,FP7-REGPOT-2011-1,STRONGER(2011), European Project: 278433,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,PREDEMICS(2011), Institut Pasteur [Paris], and Office National des Forêts (ONF)-Office National des Forêts (ONF)
Subjects: Male, RNA viruses, 0301 basic medicine, Viral Diseases, viruses, [SDV]Life Sciences [q-bio], Forests, Animal Phylogenetics, Antibodies, Viral, Pathology and Laboratory Medicine, medicine.disease_cause, Chiroptera, Zoonoses, Bats, Medicine and Health Sciences, Phylogeny, Data Management, Mammals, Ecology, Transmission (medicine), lcsh:Public aspects of medicine, Terrestrial Environments, French Guiana, Habitats, Phylogenetics, Serology, Infectious Diseases, Community Ecology, Medical Microbiology, Viral Pathogens, Vertebrates, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Neglected tropical diseases, Female, Pathogens, Brazil, Research Article, Neglected Tropical Diseases, Computer and Information Sciences, lcsh:Arctic medicine. Tropical medicine, Rabies, lcsh:RC955-962, Biology, Microbiology, Ecosystems, Rabies Virus, 03 medical and health sciences, medicine, Animals, Evolutionary Systematics, Microbial Pathogens, Ecosystem, Taxonomy, Evolutionary Biology, Ecology and Environmental Sciences, Rabies virus, Organisms, Public Health, Environmental and Occupational Health, Biology and Life Sciences, lcsh:RA1-1270, 15. Life on land, Tropical Diseases, medicine.disease, biology.organism_classification, Virology, 030104 developmental biology, Vampire bat, Lyssavirus, Zoology
Abstract: Introduction In addition to the commonly accepted importance of the vampire bat in the maintenance and transmission of the rabies virus (RABV) in South America, RABV infection of other species is widely evidenced, challenging their role in the viral cycle. Methodology / Principles findings To identify the bioecological drivers of RABV circulation in neotropical bat communities, we conducted a molecular and serological survey on almost 1,000 bats from 30 species, and a 4-year longitudinal survey in two colonies of vampire bats in French Guiana. RABV was molecularly detected in a common vampire and in a frugivorous bat. The sequences corresponded to haematophagous bat-related strains and were close to viruses circulating in the Brazilian Amazon region. Species’ seroprevalence ranged from 0 to 20%, and the risk of seropositivity was higher in bats with a haematophagous diet, living in monospecific colonies and in dense forests. The longitudinal survey showed substantial temporal fluctuations, with individual waves of seroconversions and waning immunity. The high prevalences observed in bat communities, in most habitats and in species that do not share the same microhabitats and bioecological patterns, the temporal variations, and a rather short period of detectable antibodies as observed in recaptured vampires suggest (i) frequent exposure of animals, (ii) an ability of the infected host to control and eliminate the virus, (iii) more relaxed modes of exposure between bats than the commonly assumed infection via direct contact with saliva of infected animals, all of which should be further investigated. Conclusions / significance We hypothesize that RABV circulation in French Guiana is mainly maintained in the pristine forest habitats that may provide sufficient food resources to allow vampire bats, the main prevalent species, to survive and RABV to be propagated. However, on the forest edge and in disturbed areas, human activities may induce more insidious effects such as defaunation. One of the ecological consequences is the disappearance of resources for tertiary or secondary consumers. Populations of vampires may then shift to alternative resources such as cattle, domestic animals and humans. Therefore, a good forest status, allowing both a dilution effect in highly rich bat communities and the maintenance of large populations of medium-sized and large mammals used as prey by vampires, should prevent their migration to anthropized areas., Author Summary The vampire bat is known to be the main reservoir of the rabies virus (RABV) in South America. Nevertheless, other bat species are implicated in the cycle of the virus. Indeed, seven genus-specific rabies lineages have been described in insectivorous bats in Brazil. In French Guiana, we looked for the presence of the virus in a large number of bats, belonging to 30 different species. We found a high rate of seropositive animals, mainly haematophagous bats, and in those living in monospecific colonies and in forest habitats. We also monitored two colonies of vampire bats over a 4-year period and found that some animals became seropositive for the RABV, while others, after being seropositive, were able to become seronegative. These data first of all demonstrate that the virus widely circulates in bat communities with transmission occurring via direct saliva contact with broken skin and mucosa at the intra-specific level in vampire bat species. Exposure of other bat species, including those that do not share the same microhabitat, occurs in all forest strata through modes of transmission that have yet to be determined. Secondly, these animals seem to be exposed regularly, and most of them have a great ability to control and eliminate the virus. Third, these results suggest that pristine forest habitats provide sufficient food resources for the survival of vampire bats and propagation of RABV. In contrast, in disturbed habitats, where resources are decreasing, the vampires might have to shift to alternative resources such as cattle, domestic animals or even human beings. Altogether, the risk of rabies virus transmission may increase on the edge between forest and anthropized areas.
Published: 2016

43. Complete Genome and Phylogeny of Puumala Hantavirus Isolates Circulating in France

Author: Mathilde Couteaudier, Noël Tordo, Guillaume Castel, Dominique Pontier, Angelina Plyusnina, Frank Sauvage, Alexander Plyusnin, Jean-Baptiste Pons, Jean-François Cosson, Séverine Murri, Philippe Marianneau, Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut de Biologie Computationnelle (IBC), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Ecoevolutionary Dynamics of Infectious Diseases, LabEx ECOFECT, Laboratoire de Lyon, Unité Virologie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Department of Virology [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Ecoépidémiologie évolutionniste, Département écologie évolutive [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Biologie moléculaire et immunologie parasitaires et fongiques (BIPAR), Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire d'Alfort (ENVA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre collaborateur de l'OMS Arbovirus et Fièvres Hémorragiques virales - Stratégies antivirales (CC-OMS), Institut Pasteur [Paris], project ECOFECT (ANR-11-LABX-0048, ANR-11-IDEX-0007) - Anses (Afsset grant EST-2007-75) - EU grants FP7-261504 EDENext - FP7- 278976 ANTIGONE, European Project: 261504, Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Unité Virologie, Laboratoire de Lyon [ANSES], Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Institut Pasteur [Paris] (IP), Medicum, Department of Virology, Castel, Guillaume, Centre de Biologie pour la Gestion des Populations (CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (CIRAD) - Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro) - Institut national de la recherche agronomique [Montpellier] (INRA Montpellier) - Université de Montpellier (UM) - Institut de Recherche pour le Développement (IRD [France-Sud]), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (CIRAD) - Institut National de la Recherche Agronomique (INRA) - Institut National de Recherche en Informatique et en Automatique (Inria) - Université de Montpellier (UM) - Centre National de la Recherche Scientifique (CNRS), UR Infectiologie animale et Santé publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Laboratoire de Biométrie et Biologie Evolutive (LBBE), Université Claude Bernard Lyon 1 (UCBL) - Institut National de Recherche en Informatique et en Automatique (Inria) - Centre National de la Recherche Scientifique (CNRS), Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail (ANSES Maisons-Alfort), Haartman Institute, Institut National de la Recherche Agronomique (INRA) - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) - Ecole Nationale Vétérinaire d'Alfort - AFSSA, ANR-11-IDEX-0007-02/11-LABX-0048, ECOFECT, Dynamiques eco-évolutives des maladies infectieuses(2011), European Project : 261504, EC:FP7:HEALTH, FP7-HEALTH-2010-single-stage, EDENEXT(2011), and European Project : 278976, EC:FP7:HEALTH, FP7-HEALTH-2011-two-stage, ANTIGONE(2011)
Subjects: Male, Disease reservoir, [SDV]Life Sciences [q-bio], TULA, lcsh:QR1-502, Sequence Homology, phylogeny, Puumala virus, lcsh:Microbiology, INFECTION, Nephropathia epidemica, Cluster Analysis, biology, Arvicolinae, MAJOR ANTIGENIC DOMAIN, 3. Good health, [SDV] Life Sciences [q-bio], Bank vole, Phylogeography, Infectious Diseases, diversité génétique, ANALYSIS RESOURCE, RNA, Viral, Female, France, Hantavirus, GENETICS, BIOINFORMATICS DATABASE, Molecular Sequence Data, complete genome, Zoology, Genome, Viral, analyse phylogénétique, Article, diversity, Phylogenetics, Virology, Genetic variation, medicine, Animals, Disease Reservoirs, technique elisa, VIRUS NUCLEOCAPSID PROTEIN, STRAINS, Sequence Analysis, DNA, biology.organism_classification, medicine.disease, MOLECULAR EVOLUTION, PATTERNS, campagnol roussatre, 3111 Biomedicine
Abstract: Puumala virus (PUUV) is the agent of nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) in Europe. NE incidence presents a high spatial variation throughout France, while the geographical distribution of the wild reservoir of PUUV, the bank vole, is rather continuous. A missing piece of the puzzle is the current distribution and the genetic variation of PUUV in France, which has been overlooked until now and remains poorly understood. During a population survey, from 2008 to 2011, bank voles were trapped in eight different forests of France located in areas known to be endemic for NE or in area from where no NE case has been reported until now. Bank voles were tested for immunoglobulin (Ig)G ELISA serology and two seropositive animals for each of three different areas (Ardennes, Jura and Orleans) were then subjected to laboratory analyses in order to sequence the whole S, M and L segments of PUUV. Phylogenetic analyses revealed that French PUUV isolates globally belong to the central European (CE) lineage although isolates from Ardennes are clearly distinct from those in Jura and Orleans, suggesting a different evolutionary history and origin of PUUV introduction in France. Sequence analyses revealed specific amino acid signatures along the N protein, including in PUUV from the Orleans region from where NE in humans has never been reported. The relevance of these mutations in term of pathophysiology is discussed.
Published: 2015

44. Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations

Author: Jacky Aubineau, David Fouchet, Francis Berger, Yves Léonard, Stéphane Bertagnoli, Brigitte Peralta, Jérôme Letty, Dominique Pontier, Jean-Sébastien Guitton, Stéphane Marchandeau, Alain Roobrouck, Jacqueline Gelfi, Ecoépidémiologie évolutionniste, Département écologie évolutive [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), ANR SEST program 'Pathocenoses et emergence des maladies transmissibles: un concept unificateur mis a l'epreuve sur des maladies exemplaires', Universite de Lyon by the French National Research Agency (ANR) [ANR-11-LABX-0048, ANR-11-IDEX-0007], Marchandeau, Stephane, Pontier, Dominique, Guitton, Jean-Sebastien, and Bertagnoli, Stéphane
Subjects: 0106 biological sciences, Immunity, Herd, Male, système immunitaire, immunité maternelle, [SDV]Life Sciences [q-bio], Myxoma virus, Enzyme-Linked Immunosorbent Assay, myxomatose, Adaptive Immunity, Antibodies, Viral, 010603 evolutionary biology, 01 natural sciences, Herd immunity, oryctolagus cuniculus, 03 medical and health sciences, Immune system, Immunity, Myxomatosis, Infectious, medicine, Animals, lapin, 030304 developmental biology, 0303 health sciences, Myxomatosis, General Veterinary, biology, Research, Age Factors, biology.organism_classification, Acquired immune system, medicine.disease, Virology, veterinary(all), 3. Good health, Immunoglobulin M, Infectious disease (medical specialty), Immunoglobulin G, Immunology, biology.protein, Female, France, Rabbits, Antibody
Abstract: Affiliations + remerciements ECOFECT; International audience; : The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen.
Published: 2014

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